A multicenter long-term trial comparing doxazosin and nitrendipine in the treatment of mild to moderate essential hypertension associated with hypercholesterolemia

The objective of this study was to compare the efficacy and tolerability of doxazosin, a selective alpha₁ antagonist, versus nitrendipine, a calcium channel blocker, in 80 patients with mild to moderate hypertension associated with hypercholesterolemia. During this single-blind parallel trial, blood pressure, heart rate, serum lipid levels, and hematochemical parameters were monitored for 24 weeks. Both drugs were shown to be effective in lowering supine and standing blood pressure. Nitrendipine significantly increased heart rate (P < 0.0001) while only doxazosin exerted a significant and positive effect in lowering cholesterol and triglycerides (P < 0.0001). Moreover, doxazosin decreased low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL), while the opposite was observed with nitrendipine. Less frequent and less severe adverse reactions were observed in the doxazosin group (three not clearly drug-related in the doxazosin group, 14 drug related in the nitrendipine group). The results of this study indicate that both drugs were effective in lowering blood pressure. A decrease in serum cholesterol was observed only in those patients treated with doxazosin. Furthermore, the incidence of side effects in patients treated with doxazosin was lower compared with those on nitrendipine. These data appear to encourage the use of doxazosin in the treatment of hypertension associated with hypercholesterolemia.     

Determination and comparison of the pressor effect of tyramine during long-term moclobemide and tranylcypromine treatment in healthy volunteers

Monoamine oxidase inhibitors can elicit increases in systolic blood pressure after tyramine ingestion (cheese effect). Moclobemide is a new, reversible, preferential monoamine oxidase A inhibitor with antidepressant properties. Its potentiation of the tyramine pressor effect during 200 mg t.i.d. chronic treatment was compared with tranylcypromine, 10 mg b.i.d., in a double-blind, parallel-group, placebo-controlled study (n = 16). Tyramine was mixed with food and ingested in increasing daily doses, during a normal meal, until a systolic blood pressure increase of at least 30 mm Hg was achieved (tyramine 30). When compared with the usual fasting oral tyramine tests performed in the same subjects, the mean tyramine 30 dose with a meal was 2.8 times higher. The mean tyramine 30 dose with a meal decreased from 1450 mg (range, 800 to 2000 mg) during placebo to 306 mg (range, 150 to 500 mg) during moclobemide (factor, 5.0) and from 1200 mg (range, 1000 to 1600 mg) during placebo to 35 mg (range, 20 to 50 mg) during tranylcypromine (factor, 38.2). The duration of the systolic blood pressure increase was longer with tranylcypromine (126 minutes) than with moclobemide (69 minutes) (p less than 0.01).     

Long-term treatment of essential arterial hypertension with nitrendipine

The efficacy and safety of long-term treatment with oral nitrendipine were evaluated in 34 patients with essential arterial hypertension. Nitrendipine alone significantly lowered systolic and diastolic blood pressure levels in 28 patients who completed the preliminary four-week dose-setting phase. Twenty-one patients completed the one-year treatment. Blood pressure control was maintained by nitrendipine alone in 11 patients. Ten patients not adequately controlled at the end of the dose-setting phase were successfully treated with nitrendipine combined with acebutolol or muzolimine. It is concluded that nitrendipine is a promising calcium antagonist for the treatment of arterial hypertension.     

Cerebrovascular responses to cold pressor test during static exercise in humans

The purpose of this study was to determine whether exercise modulates the responses of middle cerebral artery blood velocity (MCA V(mean)) and cerebrovascular conductance to sympathetic stimulation (i.e. cold pressor test--CPT). To accomplish this, MCA V(mean) responses were assessed during CPT, static handgrip exercise (HG) at 30% of maximum voluntary contraction and combined condition (HG + CPT), assigned in a counterbalanced order, in eight healthy subjects. Blood pressure (BP), cardiac output (CO) and end-tidal partial pressure of carbon dioxide (PETCO(2)) were also measured non-invasively, and an index of vascular conductance was calculated for MCA (CVCi). BP increased from rest (P < 0·05) during CPT and HG and was additionally augmented during HG + CPT (P < 0·05 versus rest, CPT and HG). Despite the greater augmentation in BP during HG + CPT, MCA V(mean) was similarly increased during both HG (18·5 ± 2%, P < 0·05 versus rest) and combined condition (19·6 ± 2%, P < 0·05 versus rest). MCA V(mean) remained unchanged from rest during CPT only. CVCi was slightly reduced (P < 0·05) from rest during HG but was greatly reduced by CPT (P < 0·05 versus rest). The reduction in CVCi evoked by CPT at rest (-15 ± 2%, P < 0·05 versus rest) was significantly attenuated during HG (-8 ± 2%, P < 0·05 versus CPT). Increases in CO were similar in all trials, and PETCO(2) was unchanged from rest throughout the experiments. In summary, the cerebral conductance index decreases during the cold pressure test while that reduction is smaller when the CPT is conducted during the HG. This was critical for the maintenance of MCA V(mean) during combined condition.     

Sex differences in the long-term stability of forehead cold pressor pain.

The purpose of this study was to examine sex differences in the stability of experimental pain responding across time. Stability was assessed by using 2 forehead cold pressor applications separated by 9 months. Twenty-eight men and 20 women completed both Session 1 and Session 2. Repeated measures analysis of variance showed a main effect for Session on maximum pain level. Women reported significantly more pain at Session 2, whereas men showed no difference between sessions. There were no differences on pain report between men and women at Session 1. A significant Session by Sex interaction was associated with perceived chronic stress and trait anxiety levels. At Session 2 but not Session 1, women endorsed a significantly greater expectation than men to experience unpleasant aftereffects from the cold pressor task. Additional analysis showed that chronic stress and trait anxiety were significantly associated with sex-specific pain responding. We propose that the influence of a prior painful incident on an identical repeated painful experience differs between men and women. We speculate that this influence is related to sex differences in psychological mechanisms used to interpret painful stimuli within the context of remembered experiences. To our knowledge, this is the first report of sex differences in the long-term stability of an experimental laboratory pain stimulus, controlling for follicular phase of the female menstrual cycle. PERSPECTIVE: This study examines sex differences in the stability of experimental pain responding across a 9-month period. We speculate that psychological mechanisms influence one's interpretation of a prior painful incident and that this interpretation facilitates increased pain reporting in response to an identical repeated exposure, as was observed for women.     

Effect of unclipping on pressor responses in rats with renovascular hypertension

Pressor responses to angiotensin II and noradrenaline have been examined in two models of renovascular hypertension (two-kidney one-clip and one-kidney one-clip) before and 24 h after removal of the renal artery clip to examine the possible role of pressor hyper-responsiveness in the maintenance of hypertension. Early and chronic hypertension was studied to assess the part played by progressive structural hypertrophy. Plasma renin concentration was elevated in early two-kidney hypertensive rats, whereas it was similar to that in age-matched normal rats in early one-kidney and chronic two-kidney hypertensive rats. Twenty-four hours after unclipping plasma renin concentration was the same in all groups. Unclipping restored blood pressure to normal levels by 24 h, whereas sham-operated animals remained hypertensive. Angiotensin II responses in both early and chronic two-kidney one-clip hypertensive rats were lower than in age-matched normal rats. In unclipped rats responses were similar to those in normals. One-kidney hypertensive rats had similar angiotensin II responses to normal rats and there was no change with unclipping. Blockade of endogenous angiotensin II production by converting enzyme inhibition resulted in similar angiotensin II responses in hypertensive and unclipped groups. In normal rats, angiotensin II responses were inversely related to plasma renin concentration (r = -0.47, P less than 0.001). Angiotensin II responses in hypertensive and unclipped rats were found to show a similar relationship to plasma renin concentration as normal rats. Noradrenaline responses in hypertensive rats were similar to those in age-matched normals and there was no significant change with unclipping.(ABSTRACT TRUNCATED AT 250 WORDS)     

Baroreflex sensitivity and pressor responses in a rat model of uraemia

Baroreflex sensitivity and pressor responsiveness to exogenous noradrenaline, angiotensin II and arginine vasopressin were determined in a rat model of uraemia. The slope of the regression line relating delta heart rate to delta blood pressure after phenylephrine administration was significantly less in the renal failure group than the normal control group, indicating a reduction of baroreflex sensitivity in the setting of uraemia. The pressor response to noradrenaline and angiotensin II was significantly less in the renal failure group whereas there was no difference in delta blood pressure on administration of arginine vasopressin. It is concluded that diminished baroreflex sensitivity does not contribute to the pathogenesis of hypertension in uraemia by the hypothesized mechanism of allowing the pressor effect of endogenous pressor substances to go unbuffered.     

The effects of distraction on responses to cold pressor pain

Subjective pain ratings and tolerance time were obtained during 2 cold pressor immersions for 3 groups of subjects. During the second immersion 1 group performed no task and the other 2 groups performed either an easy or difficult mental arithmetic task. The sensory-discriminative response to pain was measured by pain ratings. Pain ratings were collected every minute until subjects removed their arm from the cold pressor or until 4 min passed. Relative to a baseline cold pressor immersion, subjects in both the distraction conditions reduced their 1 min pain ratings more than control subjects. This effect was weaker at the 2 min pain rating and absent at the later ratings. The affective-reactive response to pain was measured by pain tolerance times. Tolerance time was defined as the time when subjects removed their arm from the cold pressor. Tolerance time was not altered by the distraction tasks. These findings suggest that affectively neutral distraction alters the sensory but not the reactive response to pain. Clinical implications are discussed.     

Endogenous bradykinin and the renin and pressor responses to furosemide in humans

In humans, bradykinin contributes to the acute renin response after ACE inhibition. To further explore the role of endogenous bradykinin in human renin regulation, we determined the effect of HOE 140, a specific bradykinin B(2) receptor antagonist, on the renin response to 0.5 mg/kg i.v. furosemide in a randomized, single blind, crossover design study of 10 healthy, salt-replete volunteers. HOE 140 did not affect basal plasma renin activity, aldosterone, mean arterial pressure, or heart rate. Furosemide administration increased plasma renin activity from 1.0 +/- 0.2 to 4.5 +/- 1.2 ng of angiotensin I/ml/h and there was no effect of HOE 140 (from 1.1 +/- 0.2 to 3.9 +/- 0.8 ng of angiotensin I/ml/h). Similarly, there was no effect of HOE 140 on the diuretic response to furosemide. Mean arterial pressure increased in response to furosemide after HOE 140 (82 +/- 2 to 94 +/- 2 mm Hg), but not after vehicle (81 +/- 3 to 85 +/- 2 mm Hg), whereas heart rate was unchanged. In conclusion, activation of the B(2) receptor by endogenous bradykinin does not contribute to the renin response to acute furosemide treatment in humans. However, bradykinin may contribute to blood pressure regulation under conditions in which the renin-angiotensin system is stimulated.     

Sympathetic vasoconstriction and renin secretion cause pressor responses to thyrotropin-releasing hormone in rats

To study peripheral mechanisms underlying cardiovascular responses to thyrotropin-releasing hormone (TRH) we recorded the effects of i.c.v. infusions of TRH in urethane-anesthetized rats after various drug pretreatments, nephrectomy or renal denervation. TRH invariably increased blood pressure, heart rate and sympathetic nerve activity. After alpha-1 adrenergic blockade with prazosin, pressor responses to TRH were delayed in onset and reduced in magnitude. After renal denervation or pretreatment with propranolol for beta adrenergic blockade, captopril for converting enzyme inhibition or Sar1Ile8 angiotensin II for angiotensin II blockade, pressor responses to TRH were unaltered during the first few minutes but became significantly reduced thereafter. Bilateral nephrectomy inhibited markedly the whole pressor response including its onset and subsequent elevation. Consequently, initial inhibition by prazosin was considered due to removal of alpha-1 adrenergic vasoconstriction whereas the later attenuation was attributed to antagonism of the renin-angiotensin system. None of the procedures tested affected the attendant sympathetic hyperactivity, but the tachycardia was prevented by beta adrenergic blockade. These results are compatible with the interpretation that, by acting centrally, TRH stimulates sympathetic hyperactivity which then elevates blood pressure by increasing not only sympathetic vasomotor tone but also renal renin secretion.     

Altered inotropic responses in diabetic cardiomyopathy and hypertensive-diabetic cardiomyopathy.

To understand the mechanisms of diabetic cardiomyopathy and the consequences of combined hypertension and diabetes, cardiac tissue responses to various inotropic agents were measured in experimental diabetes. Streptozotocin was injected into Wistar rats, spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Six weeks after the injection diabetic rats showed a subsensitivity to beta adrenergic stimulation in ventricular tissue and a supersensitivity and hyper-responsiveness to Ca++ and alpha adrenergic stimulation (except in WKYs) in ventricular tissues and left atria. A supersensitivity to BAY K 8644 in SHR left atria and a hyper-responsiveness to verapamil in ventricular strips were also noted. These alterations may be due to a change in receptor number or to postreceptor alterations. Diabetic SHRs exhibited greater changes in several of the drug responses (responses to isoproterenol, phenylephrine and BAK 8644) were more hyperlipidemic and had a high mortality as compared with Wistar rats and WKY diabetics. These findings confirm that the combination of hypertension and diabetes results in greater cardiac pathology than is seen with either disease alone.     

非洛地平缓释片与尼群地平治疗老年高血压疗效的比较

目的　比较非洛地平缓释片与尼群地平对老年高血压的降压疗效。方法　 42例老年原发性高血压患者随机接受非洛地平 (5～ 10mg/d)和尼群地平 (2 0～ 30mg/d) (各 2 1例 )治疗 4周。 结果　非洛地平缓释片组总有效率是 95 2 % ,尼群地平组总有效率是 85 7% (P <0 0 5 )。结论　非洛地平缓释片对老年高血压疗效明显 ,副作用少 ,耐受性好     

Differential inhibiton of alpha-1 and alpha-2 adrenoceptor-mediated pressor responses in pithed rats

The relative potencies of alpha adrenoceptor antagonists at pre- and postsynaptic receptors were assessed by comparing their effects on increments in plasma norepinephrine levels and blood pressure during stimulation of the sympathetic outflow from the spinal cord of pithed rats. Since increments in blood pressure are related to the logarithms of increases in plasma norepinephrine, the latter appear to reflect levels of the catecholamine at vascular alpha receptors. Phenoxybenzamine, dibenamine and chlorpromazine were found to block preferentially postsynaptic alpha receptors, phentolamine and tolazoline were nearly equipotent at pre- and postsynaptic receptors and mianserin and piperoxan were more potent inhibitors of presynaptic alpha receptors. Phenoxybenzamine and dibenamine were much more effective in blocking the pressor responses to sympathetic stimulation than administered norepinephrine. The opposite was true of mianserin and piperoxan, whereas phentolamine appeared to be about equipotent in blocking the pressor response to stimulation and norepinephrine. These results suggest that the pressor effects of administered norepinephrine is mediated by different receptors (alpha-2-type) than is the pressor response to stimulation of the sympathetic outflow which appears to be mediated by alpha-1-type adrenoceptors.     

Combined evaluation of pupillary and cardiovascular responses to cold pressor test in cluster headache patients

Little is known about the structures and mechanisms involved in the pathophysiology of cluster headache (CH). In this study, pupillary and cardiovascular responses to the cold pressor test (CPT) were monitored in CH patients during either an active phase of disease or a remission period in order to evaluate the oculocephalic and cardiovascular functioning of the autonomic nervous system in this form of idiopathic headache. CH patients showed a specific pattern of pupillary response on both sides during both phases of the disease. This response differed from that of controls because of an absent miosis. The pressor response to CPT was more marked in CH patients than in controls. Naloxone pretreatment caused specific and selective changes in both the pupillary and cardiovascular responses of CH patients. These data suggest a systemic sympathetic hyperactivation in response to CPT in CH patients. An oculocephalic sympathetic hypofunction is possibly associated as well as an altered opioid neuromodulation.     

Cardiovascular and endocrine responses during the cold pressor test in subjects with cervical spinal cord injuries

OBJECTIVE: To investigate cardiovascular regulation and endocrine responses during the cold pressor test in patients with chronic spinal cord injury (SCI). DESIGN: Experimental and control study. SETTING: University laboratory, department of rehabilitation medicine, in Japan. PARTICIPANTS: Eight quadriplegic subjects with complete spinal cord transection at the C6 to C8 level and 6 age-matched healthy subjects. INTERVENTIONS: Cardiovascular and endocrine responses were examined during 2 minutes of control, 3 minutes of ice-water immersion of the foot, followed by a 3-minute recovery. MAIN OUTCOME MEASURES: Blood pressure, heart rate, the Borg 15-point Rating of Perceived Pain Scale, and blood samples for measurement of plasma norepinephrine, epinephrine, plasma renin activity, plasma aldosterone, and arginine vasopressin. RESULTS: The rise in the mean arterial blood pressure during the cold pressor test in patients with SCI (baseline, 81.6+/-3.7mmHg; increased by 30%+/-6.1%) was significantly (P<.05) higher than that in healthy subjects (baseline, 101.2+/-4.5mmHg; increased by 20%+/-4.5%). The SCI subjects had no change in heart rate throughout the test, in contrast to the tachycardia noted in normal subjects. Baseline plasma norepinephrine in SCI subjects (63.0+/-18.3pg/mL) was significantly lower than in normal subjects (162.3+/-19.6pg/mL) and plasma norepinephrine increased significantly during the cold pressor test in both groups. CONCLUSIONS: In the SCI subjects, a reflex sympathetic discharge through the isolated spinal cord results in a more profound rise in mean blood pressure during ice-water immersion. This response was free of inhibitory impulses from supraspinal center and baroreceptor reflexes, either of which might restrain the increase in blood pressure.     

Cutaneous vascular responses evoked in the hand by the cold pressor test and by mental arithmetic

1. Laser Doppler flowmetry has been used to study changes in cutaneous erythrocyte flux produced in the hand (i) on successive immersion of the contralateral hand in water at 20 degrees C (cold test) and then in water at 0-4 degrees C (cold pressor test), and (ii) by mental arithmetic. 2. In 11 subjects, placing the right hand in water at 20 degrees C for 2 min induced a significant decrease in cutaneous erythrocyte flux in the contralateral hand and a significant fall in mean arterial pressure. Cutaneous vascular resistance, calculated as arterial pressure/cutaneous erythrocyte flux, showed no significant change. Thus, the decrease in erythrocyte flux was apparently due to a fall in perfusion pressure. 3. Subsequent immersion of the right hand in water at 0-4 degrees C for 2 min caused a significant decrease in erythrocyte flux in the contralateral hand and a significant rise in mean arterial pressure. It is concluded that the cold pressor response evoked from one hand elicited a substantial reflex vasoconstriction in the skin of the other hand; accordingly, calculated cutaneous vascular resistance increased significantly. 4. Eight subjects performed mental arithmetic for two periods of 2 min separated by a rest period of 2 min. By the end of the second minute of each period of mental arithmetic there was a significant decrease in erythrocyte flux. Mean arterial pressure increased significantly in the first period only, but calculated cutaneous vascular resistance increased in both periods, consistent with cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)