Echographic assessment of carotid and femoral arterial structure in men with essential hypertension

Extracoronary in vivo structural arterial changes were studied in asymptomatic essential hypertension. Carotid and femoral arteries were examined with B-mode echography for the presence or absence of plaque (the whole vascular segments of each vessel in the both sides) and for automated measurement of the far wall intima-media thickness (the vascular segment of each vessel proximal to the bifurcation in the right side) in 53 never treated hypertensive men and 133 normotensive men similar with regard to age, serum cholesterol levels, and smoking history. In the hypertensive group carotid plaque was more frequent (P < .05) and carotid and femoral intima-media thicknesses were greater (P < .001) than in the normotensive group. In the overall normotensive and hypertensive population intima-media thickness was independently associated with age and systolic pressure in both arteries (P < .001) and with cholesterol in the femoral artery (P < .05) while plaque was associated with systolic pressure (P < .01), and cholesterol (P < .01) in the carotid arteries and with age (P < .01), cholesterol (P < .05), and smoking (P < .001) in the femoral arteries. No significant difference in intima-media thickness in both arteries existed between hypertensive subjects with plaque and those without.Wall thickening and plaque were more frequent in hypertensive patients. Thickening was distributed homogeneously to both arteries, while plaque affected preferentially the femoral bed. The influence of age and pressure was more marked on intima-media thickness than on plaque. The lack of association between wall thickening and plaque suggested that vascular hypertrophy and early atherosis might be two different structural changes.     

Heart Rate Variability and Baroreflex Sensitivity in Hypertensive Subjects With and Without Metabolic Features of Insulin Resistance Syndrome

Both abnormal autonomic control of heart rate, assessed by heart rate variability (HRV) and baroreflex sensitivity (BRS), and insulin resistance syndrome are common in hypertensive patients. It is not known, however, whether abnormalities in HRV and BRS in hypertension are related to the insulin-resistance syndrome. Therefore, we compared HRV and BRS in hypertensive subjects with and without metabolic features of the insulin-resistance syndrome.HRV was analyzed using the autoregressive method from a 45-min electrocardiographic recording (15 min lying, sitting, and standing) and BRS using the Valsalva maneuver. The groups were matched for age, sex, and antihypertensive medication, and age- and sex-matched normotensive subjects served as a control group (n = 69 in each group). The insulin-resistance syndrome was defined using the criteria of 1) hypertension (blood pressure >160/90 mm Hg), 2) hypertriglyceridemia (fasting serum triglycerides ≥2.0 mmol/L), and 3) hyperinsulinemia (fasting serum insulin ≥12 mU/L).Standard deviation of RR intervals, total, very-low-, and low-frequency power of HRV were significantly lower in hypertensive subjects with insulin-resistance syndrome compared to hypertensive subjects without the syndrome and to normotensive controls (P < .001 for all), but the hypertensive group without the syndrome did not differ from the normotensive group. High-frequency power of HRV (P <.01) and BRS (P <.05) were reduced in both hypertensive groups compared to the normotensive group. In multiple regression analysis, systolic blood pressure (P <.01) and serum triglyceride level (P <.001) were independent predictors of reduced total power of HRV, but BRS was related only to systolic blood pressure (P <.01).Thus, most of the abnormalities in overall HRV seem to be confined to the subgroup of hypertensive subjects with insulin-resistance syndrome, but baroreflex and respiratory modulation of heart rate are impaired also in hypertensive subjects without metabolic features of insulin-resistance syndrome.     

Angiotensin converting enzyme gene polymorphism and activity in Turkish patients with essential hypertension

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with essential hypertension. We conducted a case-control study in Samsun, Turkey, to examine the association between ACE genotype, ACE serum activity, and blood pressure. Serum ACE activity was measured and ACE I/D polymorphism performed in 165 hypertensive and 143 normotensive subjects. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. The distribution of the DD, ID, and II ACE genotypes was 65, 77, and 23 in hypertensive patients and 42, 82, and 19 in normotensive subjects (P > .05). The estimated frequency of the insertion allele was 0.37 in hypertensive and 0.42 in normotensive subjects. Nevertheless, sensitivity analysis, based on positive family history and severity of hypertension, suggested that significant associations existed between more homogeneous groups of hypertensives and normotensives (P < .05). ACE genotype influenced ACE activity and the highest level was in DD genotype, being the lowest in II genotype. ACE serum levels were significantly higher in hypertensives as compared with normotensives (P < .01). A modest correlation was observed between blood pressure and ACE among hypertensive persons (r = 0.25, P < .05) and this did persist in multivariate analysis (P < .05 for systolic blood pressure and P < .005 for diastolic blood pressure). These data suggest that ACE DD genotype may have predisposing effects on severe hypertensives and cases with positive family history, and that ACE may be one of the independent factors on hypertension.     

Familial burden of hypertension and its effect on blood pressure levels,insulin resistance,and intracellular ions in Greek offspring

We examined the effect of familial burden of hypertension on blood pressure (BP) levels, insulin resistance (IR), and intracellular ions in healthy offspring of Greek families with one, two, or no hypertensive parents. A total of 118 adolescents and young adults were recruited. Three groups were formed: Group A, both parents were normotensive (N-N); Group B, one parent normotensive and one hypertensive (N-H); and Group C, both parents hypertensive (H-H). BP levels, homeostasis assessment model-IR (HOMA-IR) index, and intracellular Na⁺, K⁺, Ca²⁺, and Mg²⁺ were compared in the three groups. Also, multiple regression analyses were used to create models with BP parameters and HOMA-IR as dependent variables. Offspring of H-H parents had higher body mass index (BMI) (mean difference, 4.3 ± 0.9 kg/m²; 95% confidence interval [CI], 2.0–6.5), higher systolic blood pressure (SBP) (mean difference, 13.2 ± 3.1 mm Hg; 95% CI, 5.8–20.7), increased levels of intraerythrocyte Ca²⁺ (mean difference, 0.02 ± 0.01 mmol/l; 95% CI, 0.05–0.1), and fasting blood glucose (mean difference, 0.31 ± 0.10 mmol/l; 95% CI, 0.05–0.56) when compared with those with no parental history of hypertension. In the regression model, SBP was found to be significantly affected by BMI (β = 0.43; P < .001), iK⁺ (β = ?0.224; P < .01), and gender (β = ?0.298; P < .001). The addition of the parental history showed a significant independent association of H-H parental history with SBP (β = 0.27; P < .05). HOMA-IR was significantly determined by BMI (β = 0.511; P < .05), iNa⁺ (β = 0.211; P < .05), and iMg²⁺ (β = ?0.205; P < .05). Parental history of hypertension did not influence the HOMA-IR index. This study highlights the relative importance and contribution of environmental and genetic influences on the development of high BP. Both these influences possibly alter the intracellular ionic environment. However, nurture rather than familial hypertension burden is the key factor of IR in Greek offspring.     

Relationship Between Blood Pressure Variability and Serum Dehydroepiandrosterone Sulfate Levels

Decreased diurnal blood pressure variability and low dehydroepiandrosterone sulfate (DHEAS) levels are important predictors of cardiovascular morbidity and mortality. The aim of the study was to determine the relationship between DHEAS levels and diurnal blood pressure variability in normotensive subjects and in patients with essential hypertension of both genders. An ambulatory blood pressure monitor (ABPM), Meditech O2 device and radioimmunoassay were used for ambulatory blood pressure monitoring and the determination of DHEAS levels, respectively. A close correlation (P < .001) was found between the diurnal indices and plasma DHEAS levels of the 387 subjects (86 normotensive and 301 hypertensive patients) participating in the study. Decreased plasma DHEAS levels were associated in both genders, and in both normotensive and hypertensive patients with significantly (P < .001) lower diurnal indices. There was a close correlation (P < .001) between the age-related decrease in plasma DHEAS levels and diurnal indices in both genders. Systolic and diastolic blood pressure variability changed parallel to plasma DHEAS levels in both genders, whether hypertension was present or not. Additional investigations are needed to find out whether reduced DHEAS levels play a role in decreased diurnal indices or whether both can be traced back to one and the same cause.     

A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension

BackgroundBoth obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension.MethodsWe measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 μg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 μg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 ± 3.6 kg/m²). Fifteen healthy Japanese normotensive individuals were recruited as a control group.ResultsIn obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 ± 15.0 to 73.2 ± 13.5 kg (P < .01), the mean blood pressure from 118.4 ± 8.7 to 105.7 ± 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 ± 22.8 to 64.8 ± 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 ± 0.76 to 4.67 ± 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 ± 0.48 to 3.29 ± 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of N^G-monomethyl-l-arginine (8 μmol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction.ConclusionsThe present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.     

Renal macrostructure and cortical circulation in hypertension assessed by dynamic computed tomography

The aim of this study was to assess the macrostructure of the kidney and the grade of heterogeneity in renal cortical circulation in the early stages of essential hypertension. The subjects consisted of 84 patients (<50 years old) who underwent dynamic computed tomography (CT) because of various abdominal diseases and who had no serious hemodynamic abnormalities. The volumes of the whole kidney, cortex, and medulla were measured with the program installed in the CT instrument. In dynamic CT under appropriate conditions, the CT number of each pixel (image element) reflects the blood volume in the pixel. The means and standard deviations were calculated from the CT numbers within the renal cortex. The coefficient of variation (CV) of CT numbers was used as the index of the heterogeneity of renal cortical circulation. The volume ratio of cortex/medulla was significantly (P < .01) smaller in the hypertensive patients (0.80 ± 0.03 (mean ± SE)) than in the normotensive subjects (0.92 ± 0.03). The CV was significantly (P < .01) greater in the hypertensives (n = 23, 0.124 ± 0.008) than in the normotensives (n = 61, 0.106 ± 0.003). There was a significant correlation (r = −0.391, P < .001) between the CV of CT numbers and the volume ratio of cortex/medulla, and the relationship between the two variables was independent of other variables. These results suggest that the heterogeneity of renal cortical circulation is increased in the early stages of essential hypertension and is related to changes in renal macrostructure.     

Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension

Background

Essential hypertension is associated with enhanced LDL oxidation and impaired endothelium-dependent vasodilation. The antioxidant status is linked to the nitric oxide (NO) pathway. Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors inhibit oxidative stress and atherogenesis in experimental models; therefore we tested whether this beneficial antioxidant activity could be also clinically relevant in patients with essential hypertension.

Methods

Plasma LDL oxidizability was investigated initially in untreated normocholesterolemic patients with moderate essential hypertension without clinically evident target organ damage (n = 96) and in control normotensive subjects (n = 46). Patients were then randomly assigned into two age- and sex-matched groups to receive the new sulfhydryl ACE inhibitor zofenopril (15 to 30 mg/d; n = 48) or enalapril (20 mg/d, n = 48). LDL oxidizability was evaluated (generation of malondialdehyde, MDA) and systemic oxidative stress was evaluated by isoprostanes (8-isoPGF_2α). Asymmetrical dimethyl-l-arginine (ADMA), a competitive inhibitor of endothelial NO synthase, and plasma nitrite and nitrates (NOx) were also measured.

Results

LDL from hypertensive subjects had enhanced susceptibility to oxidation in vitro compared with that in control subjects (P < .05). Similarly, isoprostanes were significantly increased (P < .01) in hypertensive subjects versus control subjects. After 12-week treatment, MDA levels were significantly reduced by zofenopril (P < .05) but not enalapril treatment (P = not significant). Isoprostanes were normalized after zofenopril treatment (P < .03), whereas enalapril was ineffective. After treatment with both ACE inhibitors, plasma NOx concentrations were significantly reduced (P < .05). Similarly, hypertension increased ADMA concentration compared with the normotensive state, whereas ACE inihibition elicited a significant decrease. However, the reduction of ADMA concentration was significantly higher in patients receiving sulfhydryl ACE inhibition (P < .05 vs enalapril).

Conclusions

The sulfhydryl ACE inhibitor zofenopril reduces oxidative stress and improves the NO pathway in patients with essential hypertension. If confirmed in a large multicenter clinical trial, our data suggest a possible vasculoprotective effect of the compound in retarding vascular dysfunction and atherogenesis that often develops rapidly in hypertensive patients.     

Hypertension in Pregnancy Is a Risk Factor for Microalbuminuria Later in Life

The authors aimed to compare renal function by estimated glomerular filtration rate and albuminuria in 3 groups of women: nulliparous women, women with a history of normotensive pregnancies, and women with a history of at least one hypertensive pregnancy. Women who participated in the second Family Blood Pressure Program Study visit (2000–2004) and had serum creatinine and urine albumin measurements (n=3015) were categorized as having had no pregnancy lasting >6 months (n=341), having had only normotensive pregnancies (n=2199), or having had at least 1 pregnancy with hypertension (n=475) based on a standardized questionnaire. Women who reported having had at least one pregnancy with hypertension were significantly more likely to be hypertensive (75.6% vs 59.4%, P<.001), diabetic (34.2% vs 27.3%, P≤.001), and have higher body mass index (32.8 vs 30.5, P<.001) than those who reported normotensive pregnancies. There was a significantly greater risk of microalbuminuria (urine albumin‐creatinine ratio >25 mg/g) in those who reported at least one pregnancy with hypertension (odds ratio, 1.37; confidence interval, 1.02–1.85; P=.04) than in those with normotensive pregnancies, after adjusting for risk factors for chronic kidney and cardiovascular disease. Hypertension in pregnancy is associated with an increased risk of future microalbuminuria.     

Increased Inflammatory Markers Are Associated with Obesity and Not with Target Organ Damage in Newly Diagnosed Untreated Essential Hypertensive Patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age–sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers

Smoking potentiates the enhanced cardiovascular risk of hypertensive patients. Although nicotine replacement therapy is safe when used by healthy individuals to quit smoking, there is no evidence that nicotine replacement therapy is safe in hypertensive smokers. In this crossover, single-blinded, placebo-controlled study, we compared for 4 h the acute effects of transdermal nicotine on the mean arterial pressure (MAP) and heart rate (HR) of mildly hypertensive smokers treated with hydrochlorothiazide with the responses in normotensive smokers and nonsmokers monitored with Finapres and ambulatory blood pressure systems. The plasma concentrations of thromboxane B₂ (TXB₂, the stable breakdown product of TXA₂) were also measured by ELISA to assess whether transdermal nicotine acutely affects TXA₂ production. The use of 21-mg nicotine patches increased the MAP and HR in nonsmokers (from 94 ± 4 mm Hg and 69 ± 3 beats/min to 117 ± 7 mm Hg and 83 ± 3 beats/min, respectively; P < .05) as well as the MAP in normotensive smokers (from 83 ± 4 to 106 ± 7 mm Hg; P < .05). However, MAP and HR remained unaltered in hypertensive smokers after transdermal nicotine. Higher basal TXB₂ levels were observed in hypertensive smokers compared with normotensive smokers and nonsmokers (2019 ± 402 v 670 ± 167 and 556 ± 68 pg/mL, respectively; P < .05). Transdermal nicotine increased the TXB₂ levels only in nonsmokers (P < .05). These data indicate that the use of transdermal nicotine in mildly hypertensive smokers is probably safe. Further studies involving other classes of hypertensive patients are warranted.     

Do reduced insulin sensitivity and dyslipidemia exist in borderline hypertensive patients?

To evaluate the relationship between insulin resistance, dyslipidemia, and blood pressure (BP), we measured BP, blood glucose, plasma insulin (INS) levels, total cholesterol (T-ch), and triglyceride after an overnight fast in 454 Japanese young, nonobese, nondiabetic factory workers, including 226 normotensive (NT), 120 borderline hypertensive (BHT), and 108 essential hypertensive (EHT) subjects. Age and body mass index were strictly matched among the three groups. Fasting INS and T-ch were greater in BHT > EHT > NT (BHT ν NT, P < .05; EHT ν NT, P < .05). We also recognized significantly positive correlations between T-ch and mean BP (R = 0.39, P = .021), and between fasting INS and mean BP (r = 0.56, P = .013). These results suggests that insulin resistance and dyslipidemia are associated with hypertension in its early stage.     

Morphological changes in cavernous tissue in spontaneously hypertensive rats

Erectile dysfunction has an increased prevalence in hypertensive patients and is associated with cardiovascular diseases. For many years the discussion has been polarized on whether in hypertensive patients, it is the arterial hypertension or the antihypertensive therapy that is the cause of male erectile dysfunction. The aim of our study was to determine the morphologic changes in cavernous tissue (CT) in an animal model of arterial hypertension. Male spontaneously hypertensive rats (SHR) (n = 15) and normotensive Wistar-Kyoto (WKY) rats (n = 15) were studied for 8 months. Animals were allowed to drink tap water and fed a standard rat chow ad libitum. Systolic blood pressure (SBP) was measured monthly by the tail/cuff method. At the end of the experiment all the animals were sacrificed for microscopic studies. Cavernous tissue was processed by hematoxylin and eosin, Masson’s trichrome, and monoclonal anti-α smooth muscle actin. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) proliferation and CT fibrosis were evaluated by a semiquantitative score. SHR showed a higher proliferative score in CSM (2.7 ± 0.28 v 1.1 ± 0.07; P < .001), as well as in VSM (2.7 ± 0.25 v 1 ± 0.05; P < .001), and higher CT fibrosis score (2.8 ± 0.28 v 0.1 ± 0.07; P < .001), when compared to WKY rats. Furthermore, SHR showed a positive correlation between SBP and CSM proliferative score (r² = 0.9277), SBP and VSM proliferative score (r² = 0.8828), and SBP and CT fibrosis score (r² = 0.7775). In addition, an increase in the surrounding connective tissue at the perineurium and endoneurium of the amielinic nerves in CT was observed in the SHR group. According to these results we conclude that SHR present morphologic changes in vessels as well as in cavernous spaces of the erectile tissue that have a high positive correlation with high blood pressure. Moreover, the increase in extracellular matrix expansion seems to affect not only the interstitium but also the neural structures of the penis.     

Age-dependent regulation of renal vasopressin V1A and V2 receptors in rats with genetic hypertension: implications for the treatment of hypertension

The role of arginine vasopressin (AVP) as a hypertensive hormone remains controversial. We have previously reported that intervention with a V_1A receptor antagonist in 6-week-old prehypertensive spontaneously hypertensive rats (SHR) for 4 weeks attenuated the subsequent development of hypertension in adult SHR. This study assessed the age-dependent regulation of plasma AVP levels and kidney V_1A and V₂ receptor expression during the development of hypertension in SHR and in normotensive Sprague Dawley rats. Systolic blood pressure (SBP), plasma AVP, and plasma renin activity (PRA) and kidney V_1A and V₂ receptor expression were assessed. SHR were studied at three ages: prehypertensive (6 weeks), developed hypertension (10 weeks), and established hypertension (16 weeks). SBP increased with age in SHR (P < .01) and both plasma AVP (P < .01) and PRA (P < .05) were increased in 10-week-old SHR. Renal medulla V_1A receptor gene expression decreased in 10-week and 16-week-old SHR (P < .01), with a reduction in V_1A receptor protein in the inner medulla of 16-week-old SHR (P < .05) compared with young SHR. There was no change in V₂ receptor expression during the development of hypertension. In normotensive rats, plasma AVP, PRA, and kidney V_1A and V₂ receptor expression were unchanged over time. These data suggest that in SHR, activation of plasma AVP and the renal V_1A receptor occurs during developing hypertension, with downregulation when hypertension is established. The use of V_1A receptor antagonists in prehypertension may provide a unique opportunity for the prevention of hypertension in high-risk individuals.     

Association of Methylenetetrahydrofolate Reductase Gene 677C>T Polymorphism with Hypertension in Older Women in a Population of Buenos Aires City

We examined the relationship between the 677C >T polymorphism in the MTHFR gene and tHcy in normotensive (NT) and hypertensive (HT) subjects and the influence of sex and age in a cross-sectional study. Smoking habits, history of vascular disease, diabetes, and tHcy were significantly associated with T allele as hypertension risk factors. The T allele was significantly related with higher tHcy in (i) men versus women (P < .01), (ii) men and women older than 47 years versus the younger ones (P < .05 and P < .001, respectively), (iii) HT women versus NT women (P < .01), and (iv) older HT women versus older NT women (P < .01). We found an association between the 677C>T MTHFR polymorphism and tHcy with hypertension that in women is manifested with age.     

Increased plasma catecholamines in high renin hypertension

Plasma Catecholamines, indexes of sympathetic nervous tonicity, were measured simultaneously with renin both supine and after standing plus furosemide In patients with primary hypertension and normotensive volunteers. Seventy percent of hypertensive patients with high renin levels had increased Catecholamines compared with a 14 percent incidence in the combined group with low and normal renin (P < 0.001). Basal Catecholamines were related directly to renin in the hypertensive patients and to blood pressure in the normal (P < 0.05), but not in the high and low renin subgroups, and inversely to percent increase of catecholamines after standing plus furosemide in hypertensive and normotensive patients (P < 0.01). Sympathetic nervous hypertonicity may be responsible for the elevation of blood pressure and for the activation of the renin-angiotensin system in patients with high renin hypertension.     

Effect of insulin on renal sodium and uric acid handling in essential hypertension

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 ± 1.5 μmol/min/kg, ie, 20% lower than in normotensive controls (33.1 ± 2.1 μmol/min/kg, P = .015). In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = −0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 ± 0.12 to 1.86 ± .14 μmol/min/1.73 m², P = .0001), sodium (184 ± 12 to 137 ± 14 μmol/min/1.73 m², P = .0001), and potassium (81 ± 7 to 48 ± 4 μmol/min/1.73 m², P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.     

Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean ± SEM, 8.1 ± 0.6 v 6.8 ± 0.2 μmol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 ± 0.5 v 7.2 ± 0.5 v 8.4 ± 0.6 μmol/L; P = .148) or normotensive subjects (6.3 ± 0.4 v 8.0 ± 0.8 v 7.0 ± 0.8 μmol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.     

Is Endothelial Function of the Radial Artery Altered in Human Essential Hypertension?

There is controversy over whether endothelial function is impaired in human essential hypertension. All studies to date have used measurements of forearm blood flow by plethysmography to assess endothelium-dependent vasodilation and endothelial function. In contrast to these studies, which have focused on resistance vessels, we have determined what effects the endothelium has on underlying smooth muscle cells in conduit arteries by measuring arterial compliance of the radial arteries (change in diameter of radial artery over pressure for each arterial pulse). In 13 normotensive healthy subjects and 11 young patients with essential hypertension, arterial compliance of the radial artery was assessed directly with a new high-precision ultrasonic device (NIUS 02) after infusion of acetylcholine (endothelium-dependent response) or sodium nitroprusside (endothelium-independent response). Arterial compliance of the radial artery was similar at baseline and with increasing doses of acetylcholine and sodium nitroprusside in normotensive and in hypertensive subjects. The increase in arterial compliance from baseline at each individual concentration of acetylcholine and sodium nitroprusside was the same in both normotensive and hypertensive subjects. However, after a single oral dose of a combination of the angiotensin converting enzyme inhibitor spirapril and the calcium entry blocker isradipine, the increase in arterial compliance in response to the maximum dose of intraarterial acetylcholine was enhanced in normotensives (0.38 ± 1.23 to 0.76 ± 1.01 mm²/mm Hg × 10⁻³, P < .05), but not in hypertensives (+0.41 ± 1.26 to 0.36 ± 1.31 mm²/mm Hg × 10⁻³, not significant), and differed significantly between normotensive and hypertensive subjects (P < .05). Thus, pharmacologic stimulation disclosed a blunted response of endothelium-dependent action in the arterial compliance of the conduit arteries in hypertensive subjects. This suggests an impaired endothelial function reserve in persons with essential hypertension.