BAROREFLEX SENSITIVITY ALTERATION FOLLOWING TRANSIENT HEMISPHERIC ISCHAEMIA IN RATS: PROTECTIVE EFFECT OF ALPHAMETHYLDOPA AND GUANFACINE

The reflex tachycardia to arterial vasodilation was analysed in anaesthetized and ventilated Long Evans rats. Nicardipine was given by slow intravenous injection. The decrease in blood pressure was accompanied by a sympathetically mediated reflex tachycardia. The slope of the mean blood pressure-pulse period relationship was considered as an index of baroreflex sensitivity. Two injections of nicardipine were given during a single experiment. For studying the suprapontine control of the baroreflex arc, rats were subjected to transient (10 min) bilateral hemispheric ischaemia. These rats exhibited a blood pressure drop following recirculation and baroreflex sensitivity was impaired. Pretreatment with alpha-methyldopa, guanfacine and enalapril lowered mean blood pressure to a similar extent. In those rats pretreated with alpha-methyldopa and guanfacine transient hemispheric ischaemia did not alter baroreflex sensitivity while enalapril pretreated rats exhibited an impaired baroreflex. The protective effect of alpha-methyldopa and guanfacine against the cardiovascular consequence of hemispheric ischaemia may depend on reduced monoamine turnover resulting from central alpha-adrenoceptor stimulation.     

ATTENUATION OF PRESSOR RESPONSES TO SYMPATHETIC STIMULI IN THE RAT BY ENALAPRIL

Intravenous administration to pithed Wistar rats of the angiotensin converting enzyme inhibitor enalapril (0.1-1.0 mg/kg) lowered the diastolic blood pressure and reduced pressor responses occurring during electrical stimulation (1-30 Hz) of the spinal sympathetic outflow. These doses of enalapril given intravenously also attenuated pressor responses to intravenous injection of the muscarinic ganglion stimulant McNeil-A-343 (50, 100, 150 micrograms/kg) and noradrenaline (0.1-5.0 micrograms/kg). Enalapril (1.0 mg/kg, i.v.) reduced pressor responses to the nicotinic ganglion stimulant 1,1-dimethyl-4-phenyl-piperazinium (300 micrograms/kg, i.v.). These results confirmed that the actions of enalapril resemble those of captopril in the pithed rat, by causing reductions in both blood pressure and pressor responses to sympathetic stimuli.     

EFFECTS OF FOUR ANGIOTENSIN I CONVERTING ENZYME INHIBITORS ON REGIONAL MYOCARDIAL BLOOD FLOW AND ISCHEMIC INJURY DURING CORONARY ARTERY OCCLUSION IN DOGS

The effects of 4 angiotensin I converting enzyme inhibitors (ACEI), captopril, enalapril, ramipril, and trandolapril, were investigated on regional myocardial blood flow (RMBF, radioactive microspheres) distribution in ischemic and nonischemic zones and on ST-segment elevation in ischemic zones during intermittent coronary artery occlusion in anesthetized dogs. The 4 ACEI inhibited plasma ACE activity to an almost similar extent. All similarly reduced systemic blood pressure, an effect related to a decrease in systemic vascular resistance. Heart rate and myocardial contractility were not affected, but myocardial oxygen consumption presumably decreased because of the reduction in afterload. RMBF and their distribution (between epicardial and endocardial layers and between nonischemic and ischemic zones) were not modified by ACEI. Coronary vascular resistance was slightly decreased in nonischemic zones. ACEI had no effect on ST-segment elevation in ischemic zones. Thus, in this experimental model, all ACEI exhibited the same profile, including no change in RMBF and affording no protection against ischemic injury.     

Once Daily Dosing of Enalapril in Congestive Heart Failure

Enalapril 40 mg or tolerated dose was given once daily to 21 patients with congestive heart failure (CHF), NYHA class III, in addition to treatment with digoxin and/or diuretics. After an 8-week open period, 19 patients were randomized to continue enalapril or to receive a placebo in a double-blind manner. After the first enalapril dose of 10 mg, maximal reduction of blood pressure (BP) occurred after 4 hours (mean 34/17 mmHg; p<0.001). No further reduction was found after higher doses. After the open period significant improvement was shown as judged by NYHA class (p<0.01), stroke volume (p<0.05), maximal working capacity (p<0.05), heart volume (p<0.01) and maximum rate pressure product (RPPmax) (p<0.001). Urinary aldosterone markedly decreased (p<0.01), whereas serum potassium and serum creatinine slightly increased (p<0.05). At the end of the blind period enalapril was superior to placebo concerning NYHA class (p<0.01), heart volume (p<0.05) and RPPmax (p<0.05). Other parameters, including aldosterone in urine, did not differ between the groups. Carry-over effects may have diminished the differences between enalapril and placebo. Diarrhoea (n=5) and hypotension (n=5) were the most common side-effects. Overall, enalapril was well tolerated and seems to be useful in single daily doses in the treatment of CHF.     

TIME COURSE OF CHANGES IN BLOOD PRESSURE, ALDOSTERONE AND BODY FLUIDS DURING ENALAPRIL TREATMENT: A DOUBLE-BLIND RANDOMIZED STUDY VS HYDROCHLOROTHIAZIDE PLUS PROPRANOLOL IN ESSENTIAL HYPERTENSION

Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive. The effects of the angiotensin converting enzyme inhibitor enalapril (10-40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80-160 mg/day, p.o.) for 4 more weeks during a randomized double-blind parallel study in 14 essential hypertensives. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P less than 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.     

Comparison of enalapril and propranolol in essential hypertension

Summary In 40 patients with essential hypertension, enalapril was compared with propranolol as an antihypertensive agent in a double-blind study. The patients were randomly given either enalapril 5–10–20 mg bid or propranolol 40–80–120 mg bid in a treatment consisting of step-by-step increases in dosage. When the diastolic blood pressure remained >90 mm Hg on the highest dosage, hydrochlorothiazide was added. Both enalapril and propranolol reduced blood pressure, although the patients tended to achieve lower blood pressures while on enalapril. More patients on propranolol required additional diuretic therapy than patients on enalapril.Propranolol reduced heart rate; with enalapril there were no changes in heart rate. Both drugs increased serum potassium and urea. Plasma renin substrate was reduced by enalapril, but raised by propranolol. Enalapril increased plasma renin activity and angiotensin I, while propranolol reduced both. Converting enzyme activity was lowered with enalapril but was unchanged with propranolol. Both drugs reduced angiotensin II. Plasma aldosterone concentration was more suppressed with propranolol than with enalapril.     

氯沙坦对充血性心力衰竭患者左室质量指数的影响

目的 探讨氯沙坦对充血性心力衰竭（ＣＨＦ）患者左室质量指数和影响及其临床疗效。方法ＣＨＦ患者５１例（ＮＹＨＡ心功能分级为Ⅱ～Ⅳ级）,按照随机化区组原则分为Ａ组（氯沙坦组）和Ｂ组（依那普利组）,观察用药前及用药后１２周心功能（ＮＹＨＡ分级）、心胸比变化。心脏超声心动图仪测定用药前及用药后１２周左室舒张末期内径及左室质量指数改变。结果 ５１例充血性心力衰竭患者心胸比、左室舒张末期内径及左室量指数超过正     

EFFECTS OF ACE INHIBITION AND BETA-BLOCKADE ON COLLAGEN REMODELLING IN THE HEART OF BIO 14.6 HAMSTERS

• 1 The effects of angiotensin converting enzyme (ACE) inhibition and beta-blockade on collagen in the heart and on plasma catecholamines and tissue angiotensin (Ang) I and II were examined in Bio 14.6 Syrian hamsters. Male hamsters (76–79 days old) were given low-dose enalapril (3 mg/kg per day), high-dose enalapril (30 mg/kg per day), atenolol (50 mg/kg per day) or vehicle for 65 days. Age and sex matched healthy F₁b hamsters were used as controls. Collagen concentration was determined by measuring hydroxyproline content and the relative proportion of type I, III, and V collagens was obtained by non-interrupted sodium dodecyl polyacrylamide gel electro-phoresis (SDS-PAGE). Per cent collagen area (PCA) was measured by pixel counting in myocardial tissue by a personal computer.
• 2 Although heartweight (HW) and bodyweight (BW) in F₁b controls were significantly higher compared with drugtreated groups and vehicles, the HW/BW ratio in cardiomyopathic Bio 14.6 hamsters tended to be high compared with F₁b controls and was decreased by each drug treatment.
• 3 Collagen concentration, total collagen content and PCA in the heart of Bio 14.6 hamsters were significantly higher than F₁b controls. Collagen concentration and total collagen content were significantly decreased in all drug-treated groups compared with vehicles.
• 4 The proportion of type I collagen tended to decrease while that of type III collagen tended to increase in all drugtreated groups compared with vehicles. Type V collagen in vehicle-treated group was significantly higher than in F₁b controls, while it tended to decrease in all drug-treated groups compared with vehicles.
• 5 Plasma concentrations of catecholamines (adrenaline and noradrenaline) were decreased significantly by atenolol and high-dose enalapril, but not by low-dose enalapril. Tissue Angl remained unaltered in any of the drug-treated hamsters. Tissue Angll was decreased by the high-dose enalapril and beta-blockade, and tended to be decreased by low-dose enalapril treatment.
• 6 These results reveal that enalapril and atenolol produced similar beneficial effects on collagen remodelling in Bio 14.6 hamsters by decreasing the total amount of collagen, and also by changing collagen phenotypes through the inhibition of the renin-angiotensin system. Both drugs also improved myocardial morphological integrity.

     

依那普利联合氨氯地平对60～80岁高血压病患者血压水平及不良反应的影响

目的 分析依那普利联合氨氯地平对高血压病患者血压水平及不良反应的影响。方法 选取2017年2月—2019年2月于我院就诊的82例高血压患者,按随机数字表法分为两组,各41例,对照组采用氨氯地平治疗,观察组予以依那普利联合氨氯地平治疗,比较两组临床疗效、血压水平及不良反应。结果 观察组总有效率为97.56%高于对照的80.49%,差异有统计学意义(P<0.05);治疗前,两组血压水平对比,差异无统计学意义(P>0.05),观察组治疗后收缩压为(130.05±7.24)mmHg、24 h动态收缩压为(130.23±5.14)mmHg、舒张压为(80.47±4.38)mmHg、24 h动态舒张压为(80.11±3.54)mmHg低于对照组的(144.34±8.01)mmHg、(138.14±6.22)mmHg、(91.84±6.31)mmHg、(88.76±4.35)mmHg,差异有统计学意义(P<0.05);对照组不良反应发生率为14.63%,观察组不良反应发生率为12.20%,两组对比,差异无统计学意义(P>0.05)。结论 依那普利与氨氯地平联合应用于高血压患者中效果确切,可有效提高治疗效果,调节血压水平,且无严重不良反应发生,安全可靠,值得广泛应用。