Hemodynamic Effects of the Nitric Oxide Donor DETA/NO in Mice

(Z)‐1‐[N‐(2‐aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA/NO) is a recently synthesized member of NO‐releasing, polyamine zwitterions, the so‐called NONOates, that spontaneously liberate NO in aqueous solutions. The aim of this study was to determine the hemodynamic effects of DETA/NO in normotensive and hypertensive mice. Male Swiss Outbred mice were implanted with TA11PA‐C20 blood pressure devices (Data Sciences International, USA). After recovery (7–10 days), blood pressure was monitored for 10 days while mice were receiving saline (0.1 ml/20 g/day, s.c.). Mice were then treated every four hours for 1 day with either DETA/NO 60 mg/kg i.p. or the inactive metabolite, diethylenetriamine 38 mg/kg (molar equivalent) i.p. After a 2 week wash‐out period, mice were treated with adrenocorticotrophic hormone (ACTH: 500 µg/kg/day, s.c.) for 10 days and re‐challenged with DETA/NO or diethylenetriamine. Results were expressed as mean ± SEM. After 10 days of saline treatment, baseline systolic and diastolic blood pressure (BP) were similar for animals subsequently receiving DETA/NO or the amine (123 ± 1/95 ± 3 and 124 ± 1/92 ± 0.2 mmHg) respectively. DETA/NO induced a profound fall in BP [Systolic: 74 ± 4 mmHg (? 40 ± 3%); Diastolic: 46 ± 4 mmHg (? 52 ± 4%)] and an increase in heart rate [729 ± 33 bpm (32 ± 2%)] within the first 80 minutes. Diethylenetriamine had no effect. ACTH treatment increased BP in both groups (137 ± 16/108 ± 12 and 161 ± 1/142 ± 1 mmHg) respectively. DETA/NO induced a profound fall in blood pressure [Systolic: 92 ± 11 mmHg (? 32 ± 7%); Diastolic: 68 ± 10 mmHg (? 35 ± 10%)] and an increase in heart rate [613 ± 36 bpm (18 ± 6%)] within the first 80 minutes. Again diethylenetriamine had no significant effect. There was no significant effect on body weight with any treatment. Thus DETA/NO has potent blood pressure lowering effects in both normotensive and hypertensive mice.     

Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal continuous positive airway pressure treatment

OBJECTIVES: Effective treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (nCPAP) lowers blood pressure (BP). The long-term effects of nCPAP treatment on BP in OSA patients are not well known. The time period of such treatment sufficient to lower BP in OSA patients is also not known. We investigated compliance with long-term nCPAP therapy and its effects on BP. METHODS: This observational study involved 66 OSA patients [59 men, seven women; mean age, 51 (48-54) years; body mass index (BMI), 28.7 (27.7-29.7) kg/m; apnoea and hypopnoea, 50.3 (45.6-55.0)/h; 95% confidence intervals]. BP and BMI were measured before the study and at two checkpoints after usage of nCPAP [620 (552-688) and 1071 (1000-1143) days]. RESULTS: The different times between the first and second checkpoints for detecting objective compliance were 17 (4-30) min (P = 0.003). Diastolic BP decreased by 5.9 (3.1-8.7) mmHg after 600 days nCPAP treatment and by 4.6 (2.0-7.2) mmHg after 1000 days (P = 0.0006). Systolic BP and BMI did not change significantly. Usage of nCPAP treatment for a daily average of 3 h was needed to achieve a significant decrease in diastolic BP [7.4 (4.3-10.6) mmHg, P < 0.0001]. Diastolic BP of normotensive OSA patients did not change significantly by nCPAP treatment, but that of hypertensive OSA patients decreased significantly within 1 month-3 years of nCPAP treatment whether or not medication was used. CONCLUSIONS: In patients with severe OSA, the use of nCPAP for a daily average of 3 h would be sufficient to decrease the diastolic BP of hypertensive OSA patients.     

Lipopolysaccharide reverses adrenocorticotrophic hormone-induced hypertension in the rat.

Lipopolysaccharide (LPS) was used to stimulate nitric oxide (NO) release and investigate the effect of endogenous NO on adrenocorticotrophic hormone (ACTH)-induced hypertension in rats. After preliminary studies to determine the appropriate dose of LPS, 40 male Sprague-Dawley rats were treated with ACTH (200 microg/kg/day, s.c.) or saline (sham) for 8 days and then given a single dose of LPS (10 mg/kg, i.p.) or saline. ACTH treatment was continued for a further 5 days. Systolic blood pressure (SBP) was measured daily using the tail cuff method. Results were expressed as the mean +/- SEM. ACTH treatment significantly increased SBP (from 105 +/- 3 to 129 +/- 4 mmHg; p<0.05), whereas saline had no effect on SBP. The ACTH-induced increase in SBP was reversed by LPS injection (from 125 +/- 6 to 102 +/- 7 mmHg; p<0.05). SBP was also decreased in sham + LPS-treated rats compared with that of sham + saline-treated rats (p<0.05), but the SBP change in response to LPS was greater in ACTH-treated than in sham-treated rats (-23 vs. -8 mmHg; p<0.05). These data are compatible with the notion that reduced NO availability plays a role in ACTH-induced hypertension.     

Blood pressure and heart rate of students undergoing a medical licensing examination

AIMS: To assess the effect of a real life mental stress situation on blood pressure (BP) and heart rate (HR) in students undergoing a medical licensing examination. METHOD: Prospective observational study of 121 medical students taking the final licensing exam. BP and HR were taken before and after the exam. Additionally, BP was measured by ambulatory BP monitoring device and HR was recorded continuously by an HR monitor belt in 25 students throughout the examination. MAJOR FINDINGS: Diastolic BP (DBP) increased from 81 +/- 10 mmHg before the exam to 86 +/- 9 mmHg (p = 0.008) during the exam and to 88 +/- 11 mmHg, (p = 0.007) 15 min after the exam. Systolic BP (SBP) did not increase significantly during (from 131 +/- 14 before the exam to 136 +/- 18 mmHg) and after the exam (135 +/- 16 mmHg). HR decreased during (to 100 +/- 18 beats/min, p < 0.001), and after the exam (to 95 +/- 19 beats/min, p < 0.001) compared to values before the exam (114 +/- 19 beats/min). SBP was higher in male students compared to female students before (138 +/- 10 vs 125 +/- 18 mmHg) and after (126 +/- 18 vs 115 +/- 17 mmHg) the exam (p < 0.01). CONCLUSION: Only DBP increased during medical licensing examination, albeit within a small range. SBP did not change significantly and HR decreased during the exam. Male students showed a higher SBP compared to female students.     

Ambulatory blood pressure and neuroendocrine control after diet-assisted gastric restrictive surgery

BACKGROUND: Long-term weight control after conventional diet is disappointing but may be improved when diet is assisted by gastric restrictive surgery (GRS). OBJECTIVE: To determine the effects of GRS on ambulatory blood pressure (ABP) and neuroendocrine BP control in 28 morbidly obese subjects. METHODS: A BP and heart rate were recorded every 10 min for 25 h before and 4 months after GRS. Effects of marked reductions in body weight on the renin-angiotensinaldosterone system, on plasma insulin and on sympathetic activity were also determined. RESULTS: Body mass index decreased from 43 +/- 1 to 34 +/- 1 kg/m2 and systolic (S) BP decreased by 7 +/- 2 mmHg during daytime (P=0.01) and by 8 +/- 3 mmHg during the night (P=0.02). Pulse pressure, a marker of reduced arterial compliance, decreased by 5 +/- 1 mmHg throughout the 24 h period (P < 0.001). Diastolic BP remained unchanged. Heart rate decreased more during the night (-13 +/- 2 bpm, P<0.0001) than during daytime (-5 +/- 2 bpm, P=0.03). Reductions in SBP were largest in subjects with highest initial BP values (r = -0.63, P<0.001) but were unrelated to weight loss. GRS decreased fasting glycaemia, plasma insulin, plasma C peptide and 24 h urine sodium (n=20) and noradrenaline (n=19) excretion (P<0.01). CONCLUSIONS: Diet-assisted GRS favourably affects neuroendocrine BP control in obese patients. Reductions in sodium intake, insulin levels and sympathetic tone combined with possible improvements in arterial compliance induce persistent 24 h reductions in SBP and pulse BP. Reductions in BP are largest in subjects with highest initial BP values and are unrelated to the amount of weight loss, thereby emphasizing the importance of even moderate reductions in weight on BP control.     

Nocturnal continuous measurement of blood pressure in sleep apnea syndromes. Comparison between normotensive and hypertensive patients

Sleep apnea syndrome and systemic hypertension are frequently associated but their causal relationship is unclear. We compared the oscillations of systemic blood pressure and heart rate during polysomnography in 8 normotensive subjects (2 females) and 5 hypertensive (supine awake blood pressure: 165 +/- 7/96 +/- 5 mmHg) without treatment. Their ages (normotensive: 52.1 +/- 11.0 yrs, hypertensive: 51.2 +/- 6.4 yrs) and body mass indices (32.6 +/- 9.6 kg/m2 vs 33.2 +/- 5.2 kg/m2 respectively) were not statistically different. Systemic blood pressure was continuously monitored by a non invasive digital plethysmography (Finapres). Both groups had similar respiratory events indices (normotensive: 45.2 +/- 18.1/hr, hypertensive: 48.4 +/- 20.5/hr) and minimal oxygen saturations (79.4 +/- 9.1% vs 82.4 +/- 7.0% respectively). During apneas in slow-wave sleep were observed the minimal values for systolic and diastolic pressures which were significantly higher in hypertensive than in normotensive (138.2 +/- 9.6/83.2 +/- 16.1 mmHg vs 105.9 +/- 11.1/60.5 +/- 10.9 mmHg respectively). During resumption of ventilation maximal blood values were recorded which were also higher in hypertensive than in normotensive (185.0 +/- 13.8/113.2 +/- 21.5 mmHg vs 155.9 +/- 19.8/88.7 +/- 17.1 mmHg respectively) (p less than 0.05). Although absolute variations of blood pressure were similar, relative changes in systolic pressure were significantly higher in normotensive (p less than 0.05). Maximal heart rate was 76.8 +/- 6.2 bpm in normotensive and 76.6 +/- 3.9 bpm in hypertensive during resumption of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat

BACKGROUND: L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L-arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L-arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D-arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH-induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats.     

Two aerosolized nitric oxide adducts as selective pulmonary vasodilators for acute pulmonary hypertension

STUDY OBJECTIVES: To determine the selective vasodilatory effects of two inhaled "NONOate" aerosols in a closed chest pig model of acute pulmonary hypertension (APH). METHODS: APH was induced by IV infusion of the prostaglandin H(2)/thromboxane A(2) receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 micro mol each], or placebo (n = 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy. RESULTS: Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p < 0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p < 0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO. CONCLUSION: Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.     

The acute effect of sublingual nifedipine and isosorbide dinitrate on plasma viscosity in patients with acute myocardial infarction

The effect of sublingual nifedipine 10 mg (pierced capsule) and isosorbide dinitrate (ISDN) 5 mg on plasma viscosity (Pl.V) was investigated in 60 consecutive patients 7-10 days after hospitalization for acute myocardial infarction (AMI), who were randomized for either nifedipine (30 patients) or ISDN (30 patients). Pl.V, hematocrit (Htc), and erythrocyte sedimentation rate (ESR) were measured 20 minutes before and thereafter at 5, 10, and 30 min after drug administration while in the recumbent position. Blood pressure (BP) and heart rate (HR) were determined before each blood sample. In 18 patients (60%) Pl.V decreased by greater than 0.05 centipoise (Cp) after nifedipine (0.0953 +/- 0.033 Cp p less than 0.001 vs. initial values). After ISDN, Pl.V decreased by greater than 0.05 Cp (0.0933 +/- 0.036 Cp) in only 7 patients (23%). Systolic blood pressure (SBP) fell by 11.7 +/- 14.6 mmHg after nifedipine and by 16 +/- 14 mmHg after ISDN (nifedipine vs. ISDN = NS). Diastolic blood pressure (DBP) fell by 8 +/- 9.6 mmHg after ISDN and by 6.6 +/- 19.3 mmHg after nifedipine (nifedipine vs ISDN = NS). HR, ESR, and Htc did not change after drug administration. It is thus concluded from our study that nifedipine 10 mg sublingual has a significant Pl.V-lowering activity compared to sublingual ISDN 5 mg in patients with AMI.     

Relative deficiency of nitric oxide-dependent vasodilation in salt-hypertensive Dahl rats: the possible role of superoxide anions

OBJECTIVE: The contribution of major vasoactive systems (renin-angiotensin system, sympathetic nervous system and nitric oxide) to blood pressure maintenance and the possible involvement of superoxide anions in the reduced efficiency of nitric oxide (NO)-dependent vasodilation to counterbalance sympathetic vasoconstriction were studied in salt-hypertensive Dahl rats. DESIGN AND METHODS: We used Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) female rats kept on a low-salt (0.3% NaCl) or high-salt diet (8% NaCl) for 6 weeks since weaning. Mean arterial pressure (MAP) was measured in conscious animals subjected to acute consecutive blockade of the renin-angiotensin system (RAS) [captopril, 10 mg/kg intravenously (i.v.)], the sympathetic nervous system (SNS) (pentolinium, 5 mg/kg i.v.) and NO synthase (Nomega-nitro-L-arginine methyl ester (L-NAME), 30 mg/kg i.v.). Before the consecutive blockade of vasoactive systems one-half of the animals in each experimental group was pre-treated with a stable membrane-permeable mimetic of superoxide dismutase (tempol, 25 mg/kg i.v.) which functions as a superoxide scavenger. RESULTS: Compared to normotensive SR/Jr animals, salt-hypertensive SS/Jr rats were characterized by an enhanced blood pressure (BP) fall after ganglionic blockade (-104 +/- 8 versus -62 +/- 5 mm Hg, P < 0.001) and by higher residual blood pressure recorded after the blockade of both RAS and SNS (70 +/- 3 versus 43 +/- 3 mmHg, P < 0.01), but there was only a borderline elevation of their BP response to acute NO synthase inhibition (67 +/- 6 versus 49 +/- 4 mmHg, P < 0.05). The acute tempol pre-treatment elicited the most pronounced reduction of basal BP (-13 +/- 1 mmHg, P < 0.001) in the salt-hypertensive SS/Jr group in which the BP rise after L-NAME administration was augmented by about 50%. On the contrary, tempol pre-treatment did not affect norepinephrine- or angiotensin II-dependent vasoconstriction. CONCLUSIONS: The NO system is not able to counterbalance effectively the hyperactivity of the sympathetic nervous system in salt-hypertensive Dahl rats. The predominance of sympathetic vasoconstriction over NO-dependent vasodilation could be explained partially by enhanced NO inactivation due to augmented superoxide anion formation in hypertensive animals.     

Prevalence and mechanism of masked hypertension: the ol'mesures survey

RATIONALE: Masked hypertension (MH) and uncontrolled hypertension (UCH) have both bad prognosis. The influence of measurement circumstances on MH prevalence and reproducibility are little known. OBJECTIVE: To evaluate the prevalence and reproducibility of MH after excluding confusing factors [method and time of blood pressure (BP) measurement, antihypertensive treatment] by a standardization procedure. METHODS: 2189 hypertensive patients (61+/- 12 years, men 57%) having been treated in monotherapy by an angiotensin II receptor inhibitor for at least 8 weeks Were evaluated in a French multicenter prospective observational survey. Three BP successive office measurements were performed by the GPs during 2 visits (V) at similar times 13 +/- 9 days apart (BP: V1 149 +/- 19 / 85 +/- 11 mmHg, V2 145 +/- 19/83 +/- 11 mmHg) and home BP self-measurements (HBPM) were performed morning and evening for 3 consecutive days (HBPM morning + evening : n=18 +/- 1; 142 +/- 16/81 +/- 9 mmHg) and at the time of the visit (daytime HBPM: n=9 +/- 1; 140 +/- 16/80 +/- 10 mmHg) by the patients (Omron-705CP). RESULTS: [table: see text]. CONCLUSION: the observed MH prevalence is similar to previous published studies and is independent of: treatment, BP measurement methods, measurements frequency and HBPM time but it depends on office BP values. Consequently, its reproducibility is directly dependent of the quality of office BP measurements.     

Aspirin prevents and partially reverses adrenocorticotropic hormone-induced hypertension in the rat

BACKGROUND: Glucocorticoid-induced hypertension is associated with increased oxidative stress. The aim of the present study was to investigate the effects of aspirin, a potent antioxidant, on adrenocorticotropic hormone (ACTH) and dexamethasone (Dex)-induced hypertension. METHODS: Male Sprague-Dawley (SD) rats were treated with saline, ACTH (0.2 mg/kg/d subcutaneously) or Dex (10 mug/rat/d subcutaneously). Aspirin (100 mg/kg/d in drinking water) was given 4 days before and during glucocorticoid-treatment (prevention studies). In reversal studies, saline, ACTH, or Dex was administered for 13 days and at day 8 (T8), rats were co-administered aspirin for 5 days. Systolic blood pressure (BP) was measured by the tail-cuff method. Thymus wet weight was measured as a marker of glucocorticoid activity and lucigenin-enhanced chemiluminescence as a marker of aortic superoxide production. RESULTS: Saline or aspirin alone did not change systolic BP. Systolic BP was increased by ACTH (mean +/- SEM; from 99 +/- 2 to 133 +/- 4 mm Hg, n = 10, P < .001) and Dex (from 102 +/- 3 to 125 +/- 5 mm Hg, n = 10, P < .001). Aspirin prevented the development of hypertension caused by ACTH (P' < .01) and tended to prevent Dex-induced hypertension (P' = .07). ACTH- but not Dex-induced hypertension was partially reversed by aspirin. Both ACTH and Dex decreased thymus weight. Aspirin had no effect on thymus weight. ACTH tended to increase lucigenin-enhanced chemiluminescence (P' = .07). Aspirin had no effect on this marker of tissue superoxide production. CONCLUSIONS: Aspirin prevented and partially reversed ACTH-induced hypertension in the SD rats.     

Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW). METHODS: In 15 normotensive PMW (age 50-60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography. RESULTS: During low-salt, 24-h BP levels averaged 121 +/- 11 and 69 +/- 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol. CONCLUSIONS: Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.     

Can ambulatory arterial blood pressure monitoring taken in the 4th month of pregnancy in normotensive primaparas predict the appearance of a fetomaternal event? Results of a French multicenter study. Report of 170 cases]

OBJECTIVE: To evaluate in a primigravid normotensive population the predictive value of outcome of the ambulatory blood pressure monitoring (ABPM) at the 4th month of pregnancy. DESIGN AND METHODS: A longitudinal observational study was carried out in 174 primigravid normotensives free from proteinuria and glycosuria during the first trimester. These women underwent an ABPM (Spacelabs 90207) at 17 +/- 3 weeks gestation and were then followed up throughout pregnancy for the identification of outcome: gestational hypertension (blood pressure > or = 140/80), proteinuria, hyperuricemia, preterm delivery, birth weight < 10th percentile, need for admission to the special care neonatal unit (SCNU). STATISTICS: Non parametric tests, ROC curves. RESULTS: Of the 174 women, 170 had sufficient readings to be considered for analysis. Pre-eclampsia occurred in 5 cases (3%), gestational hypertension in 27 (16%), proteinuria in 20 (12%), hyperuricemia in 2 (1%), preterm delivery in 11 (6%), low birth weight in 9 (5%) and admission to SCNU in 16 (9%). Women with gestational hypertension already exhibited at the 4th month, both ambulatory and clinical blood pressure (BP) higher than did normotensive women (respectively: 117 +/- 7/70 +/- 5 vs 110 +/- 7/65 +/- 6 mmHg, p < 0.0001 for 24-hour ABPM, and 124 +/- 8/76 +/- 7 vs 117 +/- 10/70 +/- 9 mmHg, p < 0.005 for clinical BP). There was a non significative trend for both ambulatory and clinical values to be slightly higher in the setting of preterm delivery, proteinuria and admission to SCNU and in contrast to be slightly lower in case of low birth weight. The occurrence of one outcome or more (49 outcomes, low birth weight excepted), was associated with significantly higher ambulatory and clinical BP levels (114 +/- 7/68 +/- 6 vs 111 +/- 7/65 +/- 5 mmHg, p < 0.009 for ABPM, and 121 +/- 9/74 +/- 8 vs 117 +/- 9/70 +/- 8 mmHg, p < 0.007 for clinical BP). Positive and negative predictive values for the outcome of gestational hypertension were respectively for systolic ambulatory BP of 28% and 95% using a cut off value of 115 mmHg and for systolic clinical BP of 26% and 97% using a cut-off value of 120 mmHg. CONCLUSION: ABPM in a normotensive primigravid population at 17 weeks of gestation is not a better predictor of outcome, even of gestational hypertension, than clinical measurement.     

Circadian blood pressure variability in adrenocorticotrophin-induced hypertension in the rat

OBJECTIVES: Secondary hypertension is often characterized by loss of diurnal blood pressure variability. This study examined circadian (24 h) blood pressure variability in adrenocorticotrophin (ACTH)-induced hypertension in the Sprague-Dawley rat. METHODS: Male Sprague-Dawley rats were randomly allocated to sham (0.9% saline, s.c.), n = (9), ACTH (0.5 microg/kg per day, s.c., n = 8) or ACTH (100 microg/kg per day, s.c., n = 7) in a room with a 12 h light/dark cycle (0600 h to 1800 h). A radio telemetry transducer was used to measure blood pressure in unrestrained animals over 3 control days (C1-C3) and 10 treatment days (T1-T10). Heart rate, systolic (SBP), mean arterial (MAP) and diastolic (DBP) blood pressure were continuously recorded. Body weight was measured daily and serum corticosterone concentration ([B]) prior to death. RESULTS: Sham treatment had no effect on any parameters. ACTH 100 microg/kg per day increased SBP from 124+/-2 pooled control (PC) to 134+/-2 mmHg (T10), MAP from 105+/-2 to 115+/-2 mmHg and DBP from 87+/-1 to 99+/-2 mmHg and decreased heart rate from 305+/-6 to 249+/-5 beats/min and body weight from 299+/-6 (C3) to 280+/-8 g (T10) (all P' < 0.0036). Serum [B] was higher in ACTH- (881+/-44 ng/ml) than sham-treated rats (384+/-17 ng/ml, P < 0.001). There were no differences between sham treatment and ACTH 0.5 microg/kg per day. SBP, MAP, DBP and heart rate were consistently higher for ACTH 100 microg/kg per day and sham-treated animals during the dark cycle (1800 h to 0600 h) than the light cycle (0600 h to 1800 h). CONCLUSIONS: ACTH 100 microg/kg per day raises blood pressure in conscious unrestrained Sprague-Dawley rats without any change in normal diurnal rhythm.     

Activation of the renin-angiotensin system and blood pressure variability in rats

This study was designed to assay, using spectral analysis, the influence of the renin-angiotensin system activation on the blood pressure variability. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform local infusions and with a femoral artery catheter to measure blood pressure (BP) and heart rate (HR). The beta-adrenoceptors stimulation by isoprenaline was used to increase the plasma renin activity (PRA). A first group (n = 8) was infused with isoprenaline (0, 0.003, 10, 100, 300 ng/kg/min) at a rate of 20 microL/min. A second group (n = 8) received a bolus of the angiotensin II (AII) AT1 receptor-antagonist valsartan (2 mg/kg/mL, i.a.) prior to isoprenaline infusions. Five groups were used for blood sampling (one group infused with one concentration of isoprenaline) to assay PRA and catecholamines (CA). BP recordings were analysed using the fast Fourier transforms (FFT) on 2048 points time series (204.8 s). Isoprenaline from the concentration of 10 ng/kg/min increased PRA with a maximum effect of 8.5 fold with the highest concentration (300 ng/kg/min, p < 0.05); CA were not modified. Isoprenaline amplified the low-frequency (LF: 0.02-0.20 Hz) component of the systolic BP (SBP) variability (10 ng/kg/min: 4.16 +/- 0.62 mmHg2 versus: 2.90 +/- 0.44 mmHg2 for control value, p < 0.05) even if it did not modify BP and HR levels. Isoprenaline lowered BP and had a tachycardic effect at concentrations > or = 100 ng/kg/mL (at 100 ng/kg/mL: SBP = 115 +/- 3 mmHg, HR = 464 +/- 15 bpm, versus control: SBP = 128 +/- 3 mmHg, HR = 351 +/- 7 bpm, p < 0.05). Valsartan modified neither BP levels nor BP variability but exerted a tachycardic effect (+25 bpm, p < 0.001). Valsartan prevented the amplification of the LF oscillations of SBP induced by isoprenaline (10 ng/kg/min: 2.53 +/- 0.38 mmHg2 versus: 2.20 +/- 0.25 mmHg2 for control value (valsartan), ns). We conclude that a moderate endogenous production of renin increases SBP variability in the LF range in the conscious rat. This effect which does not affect BP and HR levels is mediated by AII AT1 receptors and does not involve the sympathetic nervous system.     

Assessement of home blood pressure with a monitor including MAM technology: comparison with the standard monitor

OBJECTIVES: To compare two periods of three days of home blood pressure monitoring (HBPM) using two different monitors with one including MAM (microlife average mode) technology. METHODS: In 152 hypertensive subjects referred to hypertension specialists, a self-measurement of blood pressure was performed sequentially with an Omron M6 (arm cuff, A/A, BHS validation) or Microlife BP-3AC1 with the MAM technology. Each patient recorded home blood pressure during two periods of 3 days with 3 measures in the morning and 3 in the evening. Order for use of each monitor was randomised. BP values were reported on a standardized document. RESULTS: In this population, aged 60 +/- 14 years, with 57% of men and a mean blood pressure of 150 +/- 21/84 +/- 21 mmHg, the home blood pressure values were 141.5 +/- 18.7/79.9 +/- 9.6 mmHg with the OMRON monitor and 138.2 +/- 17.1/79.9 +/- 10.1 mmHg with the Microlife monitor. Values between the two monitors differed about 5 mmHg for the mean SBP and about 2.8 mmHg for the mean DBP. The mean HBPM values does not differ between the two methods for more than 2.5 mmHg, 5 mmHg, 10 mmHg and 15 mmHg in 29%, 49%, 80% and 90% for SBP and in 42%, 76%, 94% and 98% for DBP respectively. CONCLUSIONS: For most of patients, mean SBP/DBP obtained with home blood pressure Measurement during three days are comparable when using monitor operated with MAM technology or not.     

Changes of blood pressure and heart rate during sexual activity in healthy adults

OBJECTIVE: This study is to observe the changes of blood pressure (BP), heart rate (HR), double product (DP) and heart rate variability during sexual activity in healthy adults before we cover patients with chronic cardiovascular disease. METHODS: Forty-nine participants grouped by sex, 22 males, aged 40.6+/-7.8 years; 27 females, aged 40.3+/-7.8 years, underwent simultaneous ambulatory monitoring of BP and HR for 24 h. During the monitoring period, sexual activity of the participants with man-on-top in their familiar environment was performed. Participants were requested to measure BP manually at the beginning of each sexual phase and three times after orgasm in every 10-min interval and 60 min after orgasm. For each individual, eight measuring values, respectively, about BP, HR, DP and heart rate variability were obtained from baseline to 1 h after orgasm. The data were statistically analyzed with paired t-test and the significant level was set at P<0.05. RESULTS: In both groups, the peak BP did not appear at orgasm, but at the beginning of plateau and dropped to baseline level at 10 min after orgasm (male 141.41+/-17.13/91.05+/-13.69 vs. 120.14+/-11.07/72.86+/-7.78 mmHg, female 121.67+/-16.61/77.37+/-15.03 vs. 109.37+/-10.54/67.19+/-9.41 mmHg). The peak HR occurred at the beginning of orgasm, and dropped to baseline level 10-20 min after orgasm (male 96.36+/-11.96 vs. 75.41+/-9.02 bpm, female 90.19+/-10.38 vs. 71.44+/-5.68 bpm). DP of both groups elevated at the beginning of plateau and orgasm then decreased to baseline level 10 min after orgasm (male 12964.27+/-2659.17 vs. 9134.09+/-1469.58 mmHg bpm, female 10044.48+/-1777.89 vs. 7841.30+/-1023.79 mmHg bpm). All the results showed that BP, HR and DP have mild to moderate changes during sexual activity in healthy adults. CONCLUSION: Using ambulatory technology to monitor BP and HR helps us to get the real data in participants during sexual activity. BP, HR and DP increase just slightly for a short time and recover to baseline level soon after sexual activity in healthy adults. The physical exhaustion during sexual activity is within the range of the daily-life workload.     

The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat

OBJECTIVE: To investigate the effects of the antioxidant Tempol on prevention and reversal of adrenocorticotrophic hormone (ACTH)-induced hypertension in the rat, a model of hypertension characterized by nitric oxide deficiency. METHODS: Male Sprague-Dawley rats (n = 10 in each group) were treated with either saline or ACTH (0.2 mg/kg per day, s.c.) for 12 days. Tempol (1 mmol/l in drinking water) treatment was started on either day 8 (T8) of ACTH or saline treatment (reversal study), or 4 days prior to ACTH or saline treatment (prevention study). Systolic blood pressure (SBP) was measured using tail-cuff sphygmomanometry. Plasma F2-isoprostanes, a marker of oxidative stress, were measured by gas chromatography-mass spectrometry. RESULTS: ACTH increased SBP (mean +/- SEM: 119 +/- 5 to 147 +/- 7 mmHg, P < 0.0005) and plasma F2-isoprostane concentration (8.4 +/- 1.2 saline versus 12.9 +/- 1.6 nmol/l ACTH, P < 0.05). Tempol alone did not alter SBP, but administration of Tempol on T8 reversed ACTH-induced hypertension (from 134 +/- 4 T8 to 118 +/- 3 mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 +/- 2 mmHg, P' < 0.05). However, Tempol had no effect on F2-isoprostane concentrations at the dose used in this study. CONCLUSIONS: ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.     

Effects of hypertension therapy based on eprosartan on systolic arterial blood pressure and cognitive function: primary results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction open-label study

BACKGROUND: Recent studies have indicated a relationship between hypertension and cognitive function but therapeutic trials of antihypertensive therapy on the prevention of cognitive disorders have produced controversial findings. METHODS: The Observational Study on Cognitive function And Systolic Blood Pressure Reduction is an open-label trial in 28 countries designed to evaluate the impact of eprosartan-based therapy on cognitive function. The Mini-Mental State Examination was used as a global tool for the comprehensive assessment of cognitive function, with an intention to treat a cohort of 25 745 hypertensive patients aged at least 50 years during a follow-up interval of 6 months. Blood pressure therapy was initiated with eprosartan 600 mg/day with provision for additional medication to be introduced after 1 month in patients with insufficient blood pressure response. RESULTS: Use of eprosartan, either as monotherapy or in combination regimens, was associated with a substantial reduction in arterial blood pressure from 161.9/93.1 mmHg at baseline to 136.1/80.8 mmHg at 6 months (P < 0.0001). The overall mean Mini-Mental State Examination score at completion of follow-up was 27.9 +/- 2.9 compared with 27.1 +/- 3.4 at baseline (P < 0.0001). A significant correlation was shown between the mean absolute response of Mini-Mental State Examination and the magnitude of systolic blood pressure reduction. At the end of the study, patients with systolic blood pressure less than 140 mmHg had a larger improvement in Mini-Mental State Examination [0.88 +/- 0.01 (SEM)] than those with systolic blood pressure between 140 and 159 mmHg [0.69 +/- 0.02 (SEM); P < 0.001], or than those with systolic blood pressure of at least 160 mmHg [0.38 +/- 0.05 (SEM); P < 0.0001]. Furthermore, cognitive decline was demonstrated in multiple linear regression to be independently associated with age [odds ratio 1.19 (1.14; 1.25)], Mini-Mental State Examination at baseline [odds ratio 1.19 (1.14; 1.25)], systolic blood pressure at baseline [odds ratio 1.20 (1.13; 1.27)] and systolic blood pressure reduction [odds ratio 0.77 (0.73; 0.82)]. CONCLUSION: The results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction are supportive of the proposition that antihypertensive therapy based on drugs that target the renin-angiotensin system is associated with preservation of cognitive function.