Neurohumoral mechanisms and left ventricular hypertrophy: effects of hygienic therapy

To determine the effects of hygienic (non-drug) therapy on blood pressure (BP) control and its relationship to sympathetic tone and left ventricular mass (LVM) in primary hypertension, plasma norepinephrine (NE) and renin activity (PRA), LVM, and nutritional and behavioral status were assessed in 76 borderline to mild hypertensives. Pretherapy plasma NE was related to diastolic blood pressure (DBP) and PRA (r = 0.24, P less than .05 and r = 0.37, P less than .01, respectively). Plasma NE of high renin patients (221 +/- 52) (mean +/- SD) was greater than that of normal renin patients (159 +/- 61, ng/l, P less than .01). LVM was related to systolic blood pressure (SBP) (P less than .001), DBP (P less than .01) and urinary sodium (P less than .05), and inversely related to PRA (P less than .01). Septal wall thickness was related to hostility (r = 0.42, P less than .05). After seven weeks of hygienic therapy, DBP was reduced by 6 mmHg (P less than .01). The change in SBP was related to baseline plasma NE (P less than .05) and inversely related to LVM (P less than .05). These results suggest that raised sympathetic tone may be a pathogenic factor in primary hypertension and that hygienic therapy lowers BP more effectively in patients with raised sympathetic tone and low LVM.     

Plasma levels of atrial natriuretic factor in mild to moderate hypertensives without signs of left ventricular hypertrophy: correlation with the known duration of hypertension

The relationship between plasma atrial natriuretic factor (ANF), blood pressure (BP), age, plasma renin activity (PRA) and urinary sodium excretion was studied in 64 normal subjects (mean age 48.7 +/- 2.1 yrs; BP: 126.5 +/- 1.6/79.5 +/- 0.9 mmHg) and in 104 untreated uncomplicated essential hypertensives (50.8 +/- 1.1 yrs; BP: 164.7 +/- 1.6/105.2 +/- 0.6 mmHg). ANF was measured by radioimmunoassay after extraction on C18 columns. ANF was significantly higher in the hypertensives than in the normal subjects (37.1 +/- 1.2 vs 29.7 +/- 1.5 pg/ml, P less than 0.01). In normals plasma ANF was significantly correlated with age (r = 0.72, P less than 0.001), Na excretion (r = 0.42, P less than 0.001) and PRA (r = -0.71, P less than 0.001) whereas in the hypertensives ANF plasma levels correlated only with systolic (r = 0.46, P less than 0.001) and diastolic (r = 0.51, P less than 0.001) BP. In addition in hypertensive patients, by multivariate linear regression analysis, a significant correlation was found between age, known duration of hypertension and plasma ANF. The partial correlation coefficient between duration of hypertension and plasma ANF was highly significant (r = 0.80, P less than 0.001). These findings suggest that in essential hypertension the level of arterial BP is a main determinant of the ANF plasma values offsetting the ability of other physiological factors to regulate plasma ANF levels.     

Role of renal kallikrein in modulating the antihypertensive effect of a single oral dose of captopril in normal- and low-renin essential hypertensives

The antihypertensive efficacy of angiotensin converting enzyme (ACE) inhibitors may result from the blockade of angiotensin II formation but also, theoretically, from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering blood pressure (BP) in patients in whom the renin-angiotensin system (RAS) is not enhanced, 31 essential hypertensives with normal or low plasma renin activity (PRA) were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall, in both systolic and diastolic BP, was obtained in the subgroup of patients who were classified as 'normal-kallikrein hypertensives' according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in 'low-kallikrein hypertensives'. Furthermore, the mean percentage fall in mean BP, throughout the 2 h following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, P less than 0.05) in all the patients. Our results suggest that blunted activity of the kallikrein system might be responsible for failure of captopril to lower BP in some hypertensive patients.     

Effect of antihypertensive treatment in elderly hypertensive patients with cardiac hypertrophy]

In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/- SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH: SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84 +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH. LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition

The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased ratio between changes in blood pressure and plasma norepinephrine in essential hypertension.

The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of plasma catecholamine levels and the pressor sensitivity to endogenous norepinephrine. The latter was estimated indirectly by the ratio between changes in blood pressure and those in plasma norepinephrine after adrenergic neuronal blockage with debrisoquine (given orally for 6 weeks). Normal subjects and patients with borderline or established essential hypertension had comparable pretreatment levels of plasma norepinephrine and epinephrine. Debrisoquine lowered plasma norepinephrine by a similar degree (almost 50%) in these three groups; in contrast, blood pressure decreased only slightly in normal or borderline hypertensive subjects [-3.4 +/- 3.2% and -5.4 +/- 1.6% (SE), respectively] but fell significantly more (P less than 0.005) in patients with established essential hypertension (-20.7 +/- 3.9%). The ratio between percentile changes in blood pressure and those in endogenous norepinephrine levels was comparable in normal and borderline hypertensive subjects (0.03 +/- 0.08 and 0.17 +/- 0.04, respectively), but increased (P less than 0.001) in established essential hypertension (0.62 +/- 0.11). This suggests that essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma norepinephrine levels with increased norepinephrine pressor sensitivity.     

Dopamine beta-hydroxylase and plasma renin activity in patients with low-, normal-, and high-renin essential hypertension.

The relationship of serum dopamine-beta-hydroxylase (DBH), plasma renin activity (PRA) and urinary catecholamines (IU catechols) in various forms of essential hypertension (EHT) (low, normal and high renin) was evaluated. Eighty-four predominantly white, young (37 +/ 8 years (SD)), mildly hypertensive patients (diastolic pressure 93 +/- 4 mm Hg (SD)) continued their regular diet and received no medications. Thirteen patients had low-renin, 64 had normal-renin, and seven had high-renin EHT. DBH, total IU catechols and urinary norepinephrine were not different between these renin subgroups. DBH was significantly lower in all hypertensives (55.6 +/- 36 IU) and in the low-renin subgroup (46 +/- 30 IU) compared with normal subjects (68 +/- 35 IU) (p less than 0.01). However, the DBH range was so broad that an individual DBH value did not distinguish EHT from normals. After a baseline period, patients were randomly assigned to receive chlorthali done 50 mg q.a.m. or placebo in a double-blind study. In the chlorthalidone group 1 month after therapy, the diastolic pressure decreased, PRA increased, and total IU catechols and urinary norepinephrine increased. Serum DBH did not change during diuretic therapy. A significant correlation could not be shown between pretreatment DBH and the changes in PRA and IU catechols before and after diuretics for all treated EHT patients. However, within the normal PRA EHT subgroup receiving chlorthalidone, the one-third of patients with lowest pretreatment DBH levels (n = 10) were compared with the one-third of patients with the highest pretreatment DBH values (n = 10). The lower DBH patients showed significantly less change in PRA (delta PRA = 2.9 +/- 1.8 ng/ml/hr) compared with the higher DBH patients (delta PRA = 8.2 +/- 1.6; P less than 0.05). In some EHT patients, DBH levels may be related to PRA response to diuretic therapy.     

The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of long acting nifedipine and enalapril in elderly hypertensives: a randomised, single-blind, cross-over study

The effects of nifedipine and enalapril on blood pressure (BP), heart rate, plasma and urine electrolyte, plasma renin activity (PRA), aldosterone and catecholamines, were studied in ten elderly hypertensive subjects in a randomised, single-blind, cross-over trial. Both nifedipine and enalapril were effective in lowering supine and erect systolic and diastolic BP, with nifedipine causing a significant (P less than 0.05) rise in heart rate. Arterial pressure rose to pre-treatment levels on withdrawal of both drugs. Plasma glucose fell significantly (P less than 0.02) on enalapril therapy, whilst no other biochemical changes were observed. PRA, aldosterone and adrenaline rose on nifedipine therapy whereas PRA showed a greater rise on enalapril with a fall in plasma aldosterone and no change in plasma adrenaline. Plasma noradrenaline was not altered by either agent. Unacceptable side effects occurred in patients taking nifedipine resulting in discontinuation of therapy in 2 patients and death in another. Nifedipine or enalapril monotherapy is effective in lowering BP in the elderly hypertensives. Although more experience is needed, the side effect profile of both agents especially enalapril, appears satisfactory.     

The antihypertensive effect of captopril in essential hypertension: relationship to prostaglandins and the kallikrein-kinin system

Two groups, each with nine essential hypertensive patients, were maintained on 10 mmol sodium daily over 14-17 days and treated in this sequence: placebo; captopril (25 or 50 mg given thrice daily) or indomethacin (50 mg given thrice daily) alone; captopril plus indomethacin, and (4) captopril alone. The initial fall in mean blood pressure induced by captopril (118 +/- 1 to 102 +/- 1 mmHg) was unaffected by the addition of indomethacin. However, if indomethacin treatment preceded captopril, the antihypertensive effect was attenuated (116 +/- 4 to 109 +/- 4), and was associated with significant reductions in urinary prostaglandin and kinin excretion. Addition of captopril to indomethacin returned kinin excretion to placebo levels but did not affect indomethacin-induced reduction in prostaglandin excretion. Captopril alone stimulated plasma renin activity (PRA) fivefold; aldosterone excretion was lowered by 25% and further reduced by indomethacin. Thus, when captopril and indomethacin are administered together, the order of administration is critical to the antihypertensive effect of captopril.     

Natriuretic hormones in young hypertensives and in young normotensives with or without a family history of hypertension.

The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute antihypertensive effect of captopril in hypertensive patients: with special reference to kallikrein-kinin system

In order to clarify the role of the kallikrein-kinin system in the hypotensive mechanisms of converting-enzyme inhibition, captopril was administered in a single oral dose of 50 mg to 17 hypertensive patients, of whom 14 had essential hypertension, one had chronic renal failure, one had primary aldosteronism, and one had glucocorticoid responsive hyperaldosteronism. Captopril lowered blood pressure remarkably in either low-renin or normal-, and high-renin hypertensives, however, there was no significant relationship between the fall in blood pressure and pretreatment levels of plasma renin activity (PRA) in any of the patients any time after the administration. PRA was significantly increased in normal- and high-renin hypertensives but not in low-renin patients. Plasma aldosterone concentration (PAC) was decreased significantly in normal- and high-renin patients, while no significant change in PAC was observed in patients with low-renin activity. Captopril elevated plasma bradykinin concentration (PBK) from a control value of 12.5 +/- 4.1 (mean +/- s.d.) to 20.3 +/- 7.7 pg/ml (p less than 0.001) at 30 min, and there was a significant correlation between changes in PBK and changes in mean blood pressure 120 min after the administration in all the patients (r = 0.741, p less than 0.01, n = 17). In one patient with primary aldosteronism, PBK increased from a baseline of 10.0 to a maximum value of 19.0 pg/ml, corresponding to the rapid fall in blood pressure. Also, in one patient with glucocorticoid responsive hyperaldosteronism, captopril increased PBK from a control of 14.1 to 27.9 pg/ml at 30 min, corresponding to the marked fall in blood pressure from 170/106 to 136/90 mmHg. From these findings, it is suggested that the accumulation of kinins following captopril administration plays a major role in the short-term reduction of blood pressure in hypertensive patients, especially in those with low renin-angiotensin activity.     

Effectiveness of furosemide in uncontrolled hypertension in the elderly: role of renin profiling

BACKGROUND: Despite many advances in the treatment of hypertension, adequate blood pressure (BP) control in elderly patients continues to be a challenge. Optimal control of BP remains elusive because of issues relating to drug dosage and proper choice of therapeutic agents, including questions regarding the role of diuretics. METHODS: We examined the effect of diuretic treatment on BP in 12 elderly hypertensive patients whose hypertension was poorly controlled on previous drug regimens. We also evaluated the relationship of systolic, diastolic, and mean arterial BP (SBP, DBP, MAP, respectively) to changes in plasma renin activity (PRA), serum aldosterone (SA), atrial natriuretic peptide (ANP), and serum chemistries both before and after adding furosemide to the prior antihypertensive agents. RESULTS: At baseline, 83% of patients had low PRA (< 1 ng/mL/h). After furosemide, in 67% of patients, decreases in SBP (166 +/- 5 to 134 +/- 5 mm Hg; P <.001), DBP (82 +/- 4 to 71 +/- 4 mm Hg; P =.004), and MAP (111 +/- 3 to 92 +/- 3 mm Hg; P <.001), were associated with increases in PRA (2.1 +/- 1.2 to 5.1 +/- 1.8 ng/mL/h; P =.01) and SA (4.8 +/- 1.0 to 9.4 +/- 1.4 ng/dL; P =.01) and with decreases in ANP (101 +/- 28 to 58 +/- 11 pg/mL; P =.01) and body weight (77.5 +/- 3.6 to 76.4 +/- 3.3 kg; P =.02), findings consistent with volume mediated/salt sensitive hypertension. In the remaining 33% of patients, BP also decreased significantly, but there was no increase in PRA (0.15 +/- 0.05 to 0.10 +/- 0 ng/mL/h) or SA (9.2 +/- 2.2 to 7.0 +/- 0.8 ng/dL) and no decrease in ANP (66 +/- 5 to 75 +/- 18 pg/mL) (P = ns for all), suggesting alternate mechanisms for their responses. CONCLUSIONS: Many of the elderly hypertensive patients in our study had decreased PRA levels and showed significant reductions in BP after furosemide administration. Despite the associated increases in PRA and SA and decreases in ANP in 67% of patients, diuretic use remains important in the control of hypertension in this population.     

Relation Between Urinary Kallikrein Excretion and Blood Pressure Response to a Single Oral dose of Captopril

Thirty-one essential hypertensives with normal or low PRA were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall both in systolic and diastolic blood pressure (BP) was obtained in the subgroup of patients who were classified as “normal kallikrein hypertensives”, while no significant change in BP was observed in “low kallikrein hypertensives”. Furthermore the mean percentage fall in mean BP, throughout the 2 hours following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47 p < 0.05) in the entire group of patients. Our results suggest that a blunted activity of the kallikrein system might be resposible for failure of captopril in lowering BP in patients in whom the renin-angiotensin system is not pathogenetically implicated.     

Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised,double-blind comparative trial in Asian patients

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P相似文献   

硝苯地平和卡托普利对高血压患者血浆、唾液、尿液心钠素浓度的影响

目的探讨心钠素（ＡＮＰ）在高血压发病中的作用。方法５２例原发性高血压（ＥＨ）患者，随机分组，应用硝苯地平或卡托普利治疗２周前后，测定血浆、唾液、尿液ＡＮＰ含量的变化，并与健康组对照。结果治疗前患者血浆、唾液、尿液中ＡＮＰ均高于对照组（Ｐ＜０．０１）。治疗２周后，高血压组ＳＢＰ、ＤＢＰ和血、唾液、尿液中ＡＮＰ较治疗前明显降低（Ｐ＜０．０１），而治疗组间比较差异无显著性（Ｐ＞０．０５），且唾液和尿液中ＡＮＰ与血浆中浓度有同样变化趋势。结论硝苯地平和卡托普利可能是通过抑制ＡＮＰ的产生和释放的某个环节而发挥其降压效果的。     

Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing

BACKGROUND: Previous studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium-channel blockers (CCBs), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the administration-time dependent antihypertensive efficacy of the slow-release, once-a-day nifedipine gastrointestinal-therapeutic-system (GITS) formulation. METHODS: We studied 180 untreated hypertensives (86 men and 94 women), 52.5 +/- 10.7 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment. RESULTS: The BP reduction after treatment was significantly larger with bedtime dosing mainly during night time sleep (P < 0.012). The number of patients with controlled ambulatory BP after treatment was greater with bedtime than morning treatment (P = 0.016). The baseline prevalence of nondipping was unaltered after ingestion of nifedipine on awakening, but reduced from 51 to 35% after bedtime dosing (P = 0.025). The morning surge of BP, a risk factor for stroke, was significantly reduced (P < 0.001) only after bedtime administration of nifedipine. Bedtime in comparison to awakening-time ingestion of nifedipine was also associated with a reduction in the incidence of edema from 13 to 1% (P < 0.001). CONCLUSIONS: The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.     

Norepinephrine and forearm vascular resistance responses to tilt and cold pressor test in essential hypertension: effects of aging

Heart rate, blood pressure, forearm vascular resistance (FVR), and catecholamine and renin responses to head-up tilt at 80 degrees and cold pressor test were investigated in 15 hypertensive men aged less than fifty-five (mean 44 +/- 7 years; M +/- SD) and 13 similarly hypertensive men aged more than fifty-five (mean 62 +/- 4 years; M +/- SD). Baseline plasma norepinephrine levels, as well as norepinephrine responses to tilt and cold pressor stress, were similar in the two groups, suggesting a lack of age-related increase in plasma norepinephrine (NE) responses in patients with essential hypertension. Normalized FVR responses (% change) to tilting (28 +/- 21 vs 95 +/- 36; M +/- SE) and cold pressor test (33 +/- 12 vs 64 +/- 21; M +/- SE) were significantly less (p less than 0.01) in older hypertensives. These results, but not the plasma NE responses to reflex sympathetic activation by tilt and cold pressor testing in older hypertensives, suggest an impaired forearm vasoconstriction.     

Depressor effects of captopril in DOCA-salt hypertensive rats: role of vasopressin

Oral administration of the angiotensin I-converting enzyme inhibitor captopril produced a substantial reduction of blood pressure in DOCA-salt hypertensive rats. After oral administration of captopril (30 mg/kg), mean blood pressure decreased from 172 +/- 11 to 148 +/- 9 mmHg (P less than 0.01) in one hour and its antihypertensive effects lasted for the next seven hours. Plasma vasopressin levels showed a marked elevation in DOCA-salt hypertensive rats compared with control values (22 +/- 5 versus 5 +/- 3 pg/ml). This increase in vasopressin was significantly reduced by captopril from 25 +/- 5 to 8 +/- 6 pg/ml. In addition, whole body vascular reactivity to norepinephrine was examined. Responsiveness was at first attenuated but returned to control value in spite of reduction of both plasma vasopressin and blood pressure. Thus, captopril reduces blood pressure in DOCA-salt hypertensive rats and the fall in blood pressure is accompanied by reduction of plasma vasopressin and attenuation of vascular reactivity.     

Lack of reflex increase in myocardial sympathetic tone after captopril: potential antianginal effect

Many vasodilators have been tried as antianginal agents, but the reflex increase in sympathetic tone produced by these drugs necessitate their use with caution in patients with angina. In the first part of this study, captopril was given to 14 patients with angina and systolic arterial pressures of greater than 120 mm Hg. Over the short term, captopril decreased arterial blood pressure (from 110 +/- 18 to 98 +/- 18 mm Hg, p less than .01) without increasing heart rate (75 +/- 15 vs 74 +/- 15 beats/min), arterial concentrations of epinephrine (0.38 +/- 0.28 vs 0.34 +/- 0.25 nM) or norepinephrine (2.7 +/- 2.1 vs 2.8 +/- 2.1 nM), or transmyocardial norepinephrine balance (216 +/- 254 vs 146 +/- 170 p mol/min). Captopril decreased average myocardial oxygen consumption (9.7 +/- 4.1 to 8.2 +/- 2.7 ml/min, p less than .01). Given over the long term (mean 5.5 months), captopril decreased the severity of angina from NYHA classification 3.0 +/- 0.8 to 1.6 +/- 0.8. In the second part of this study, captopril was given in a prospective, randomized, double-blind, placebo-controlled study to 21 patients with stable exercise-induced angina and systolic arterial pressures greater than 120 mm Hg. Captopril increased exercise time (309 +/- 137 vs 374 +/- 142 sec, p less than .05) without changing anginal threshold (rate-pressure product 17.0 +/- 6.0 vs 17.1 +/- 5.6 X 10(-3)). We conclude that captopril decreases mean arterial pressure without causing a reflex increase in myocardial sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)