title: Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension.
abstract: Recent experimental studies showed that inhibition of angiotensin II synthesis may reduce sympathetic activity as evaluated by plasma catecholamine assay, sharing in the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Fifteen patients with essential hypertension were studied. Blood pressure and heart rate were evaluated both at rest and after stressor laboratory tests, before and four hours after administration of 20 mg of enalapril maleate and on the 14th and 120th days of continued administration. At the same time, blood samples were drawn for determinations of plasma renin activity, ACE, angiotensin II, plasma aldosterone concentration, and plasma norepinephrine levels. Enalapril in a dosage of 20 mg/day significantly and progressively lowered systolic and diastolic blood pressure at rest, with maximal decreases observed on the 120th day of the study period (P less than 0.001). Heart rate at rest and after exercise showed no significant differences throughout the study period. Good blood pressure control was observed during stressor laboratory tests. The greatest impact of blood pressure was observed on the 120th day during dynamic exercise (mean blood pressure from 139 +/- 3.9 to 111.5 +/- 6.3 mmHg; P less than 0.01) and on the 14th day during the cold pressure test (mean blood pressure from 133.3 +/- 3.9 to 111.2 +/- 4.7 mmHg; P less than 0.005). A marked and persistent ACE inhibition and a gradual and progressive decrease of angiotensin II (from 12.42 +/- 2.15 to 5.45 +/- 1.68 pg/ml; P less than 0.005) characterized the humoral activity of enalapril maleate. Moreover, a significant decrease of plasma norepinephrine levels was observed during the follow-up period with maximal reduction on the 120th day (from 311 +/- 34 to 197 +/- 33 pg/ml; P less than 0.01). It has been demonstrated that the pressor effect of angiotensin II was blunted during exercise. Our hemodynamic and humoral results appear to confirm the hypothesis that enalapril maleate may reduce blood pressure by direct inhibition of ACE and of kininase II as well as by a decreased sympathetic output, which may be secondary to angiotensin II inhibition. These results agree with the recent experimental demonstration of a reduced sympathetic nervous response to nerve stimulation during ACE inhibition.
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004656:Enalapril / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D012083:Renin; D009638:Norepinephrine