Captopril-treated Group Research Articles

Lack of effect of indomethacin and captopril on protein-induced glomerular hyperfiltration in normal subjects.

We examined the possible roles of renal prostaglandins, renin-angiotensin and the kallikrein-kinin system in protein-induced glomerular hyperfiltration in normal subjects. The normal subjects were divided into three groups, i.e., control, indomethacin-treated and captopril-treated groups. Protein loading (0.6 g/kg BW as protein) resulted in a significant increase in glomerular filtration rate (GFR) from a baseline of 98 +/- 8 ml/min/1.73 M2 to 135 +/- 13 (P less than 0.01) in the control group. In both the indomethacin and captopril groups, significant elevations of GFR were observed after the test meal. The urinary kallikrein excretions after the meal were not significantly different from those for preloading in all groups. These results suggest that renal prostaglandins, renin-angiotensin and the kallikrein-kinin system may be less involved in protein-induced glomerular hyperfiltration in normal subjects.

Role of renin-angiotensin system in the pathogenesis of spontaneous myocardial fibrosis in Sprague-Dawley rats: effect of long-term administration of captopril.

The role of endogenous renin-angiotensin system in the pathogenesis of spontaneous myocardial fibrosis in male and female Sprague-Dawley rats was examined by long-term inhibition of endogenous angiotensin II production. For this purpose captopril, angiotensin I converting enzyme inhibitor (ACEI), was given at 30 or 100 mg/kg/day mixed with commercial powdered standard diet (CE-2, Japan Clea Co., Tokyo) for 52 weeks. Myocardial lesions consisting of focal fibrosis and minute necrotic foci of muscle cells intermingled with monocytic infiltration appeared preferentially in the subendocardial areas of the left ventricle. The incidence of myocardial fibrosis was very low in female rats, but in male rats, the incidence and severity of the lesion was significantly reduced in the captopril-treated groups than in the control group. These findings suggest that endogenous angiotensin II acts as a facilitatory effect on the pathogenesis of spontaneous myocardial lesion which can be effectively reduced by long-term administration of nontoxic dose of ACEI. The authors speculate that ACEI may have a therapeutic use in clinical cases of idiopathic myocarditis.

Functional infarct expansion, left ventricular dilation and isovolumic relaxation time after coronary occlusion: A two-dimensional echocardiographic study

Left ventricular dilation and infarct expansion after acute myocardial infarction are associated with an increased morbidity and mortality. The purpose of this study was to determine whether angiotensin-converting enzyme inhibition could reverse left ventricular dilation and improve the diastolic properties of the left ventricle very early after coronary occlusion. The acute time course of left ventricular dilation and infarct expansion (as determined by two-dimensional echocardiography) and early diastolic isovolumic relaxation time were studied in 20 dogs subjected to 3 h of coronary occlusion. End-diastolic area before occlusion was 8.4 ± 0.5 and 8.9 ± 0.7 cm2(p = NS) in the captopril- and the saline-treated group, respectively. At 30 min after occlusion (pretreatment), end-diastolic area increased to 12.6 ± 0.8 cm2in the captopril-treated group (p < 0.01) and 11.3 ± 0.9 cm2(p < 0.05) in the saline-treated group. Three hours after occlusion and after captopril treatment, end-diastolic area decreased to 9.4 ± 0.6 cm2(p < 0.05 versus 30 min after occlusion), whereas it was unchanged in the saline-treated group.Functional infarct expansion (as assessed by end-systolic anterior to posterior endocardial segment length ratio) occurred early after occlusion, and captopril reduced this expansion. Pretreatment values for early diastolic isovolumic relaxation time increased from 29.1 ± 2.4 to 50.5 ± 2.9 ms in captopril-treated dogs (p < 0.01) and from 34.3 ± 3.4 to 46.9 ± 2.7 ms in saline-treated dogs (p < 0.01) after coronary occlusion, implying a worsening of diastolic function. Early diastolic isovolumic relaxation time was significantly decreased from 50.5 ± 2.9 to 38.9 ± 3.1 ms (p < 0.01) with captopril, whereas it remained unchanged after treatment with saline solution. Thus, two-dimensional echocardiography can detect early left ventricular dilation and infarct expansion after coronary occlusion. Captopril favorably influences these acute topographic changes and improves diastolic relaxation.

Factors controlling aldosterone secretion during hypoxemia in fetal lambs.

Factors modulating the fetal aldosterone response to hypoxemia were studied in three groups of chronically catheterized fetal lambs between 131 and 143 days of gestation (term, 145 days). One group (control group) received an infusion of 5% dextrose in water; the second group (captopril-treated group) was given captopril, an inhibitor of angiotensin-converting enzyme; the third group (captopril plus dexamethasone-treated group) received dexamethasone in addition to captopril. In all groups of fetuses, hypoxemia was associated with a significant increase in plasma K+ concentration (+0.7 +/- 0.1 meq/liter). In control fetuses, changes in plasma aldosterone concentration during hypoxemia correlated closely with changes in plasma K+ concentration r = 0.79; P less than 0.001) and with changes in plasma angiotensin II concentration (r = 0.77; P less than 0.001). In the captopril-treated fetuses, the rise in plasma aldosterone concentration during hypoxemia correlated closely with plasma K+ (r = 0.79; P less than 0.001) but not with plasma angiotensin II values (r = 0.17). No significant correlation was found between percent changes in maternal aldosterone and percent changes in fetal aldosterone during hypoxemia and following recovery (r = 0.36; P greater than 0.1) in captopril-treated fetuses. Administration of dexamethasone to fetuses receiving captopril completely inhibited the rise in plasma aldosterone associated with hypoxemia. Taken together, the present results suggest that the rise in plasma aldosterone during hypoxemia is not related to the level of activity of the renin-angiotensin system but depends probably on the increased secretion of adrenocorticotrophin by the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the renin-angiotensin system in the development of congestive heart failure in the dog as assessed by chronic converting-enzyme blockade

Hormonal factors may be important in the regulation of peripheral vascular resistance (PVR) in congestive heart failure (CHF). The role of the renin-angiotensin system in the development of CHF was studied in 16 unanesthetized dogs. CHF was induced by rapid right ventricular pacing, with and without chronic converting-enzyme inhibition (CEI) by captopril. The hemodynamic changes and the activity of renin, aldosterone, norepinephrine and vasopressin were studied. The control dogs showed a greater decrease in cardiac output and a greater increase of mean pulmonary artery pressure than the captopril-treated group. In the group with CEI, only a small, transient increase in PVR was observed during the development of CHF; in the control group, there was an increase of 94% of basal values. The control group showed a continual increase of renin, aldosterone and norepinephrine. Four control dogs showed an inappropriately high secretion of arginine vasopressin. The increase of sympathetic nervous activity was only insignificantly attenuated by angiotensin II inhibition and was without a considerable influence on PVR except for an early transient increase in vascular tone. In our animal model, the renin-angiotensin system plays an important role in the regulation of PVR in CHF. In this kind of CHF the sympathetic nervous system appears to be of minor importance for the long-term regulation of PVR. Plasma arginine vasopressin levels were increased in control dogs; this increase may contribute to the increased vascular tone.

Effect of converting enzyme inhibition on pulmonary edema after microembolization.

We examined the effect of converting enzyme inhibition with captopril (SQ 14,225) on pulmonary hemodynamics and on accumulation of extravascular lung water after microembolization in dogs. Pulmonary microembolization, induced with glass beads (200 microns diam), increased the mean pulmonary arterial pressure to approximately 40 Torr in both control and captopril-treated animals. The increase in pulmonary vascular resistance (PVR) in control animals was sustained during the 75 min of study and was associated with an increase in the extravascular lung water content-to-bloodless dry lung weight ratio (W/D) from a normal value of 2.84 +/- 0.22 to 4.53 +/- 0.24 ml/g (P less than 0.01) after embolization. In the captopril-treated group, the PVR increased gradually, such that the value at 75 min postembolization was greater than in controls (P less than 0.05). The W/D in the captopril-treated group of 4.62 +/- 0.19 ml/g was greater than the value of 2.83 +/- 0.10 ml/g in nonembolized captopril-treated animals, but the degrees of edema in the control and captopril-treated animals were not different. A similar degree of embolization induced during infusion of 5 micrograms X kg-1 X h-1 of bradykinin also did not enhance the pulmonary edema, and there was also a greater increase in PVR than in control animals after embolization. These findings suggest that bradykinin does not contribute to the degree of pulmonary edema after microembolization.

Captopril: Evaluation of Low Doses, Twice-Daily Doses and the Addition of Diuretic for the Treatment of Mild to Moderate Hypertension

1. We randomized 475 men whose diastolic blood pressure was 92–109 mmHg to either placebo- or captopril-treated (37.5, 75 and 150 mg/day) groups for 7 weeks. 2. After 7 weeks, the placebo-treated patients were given hydrochlorothiazide (25 mg twice daily), as were two-thirds of each captopril-treated group, and they were observed for 7 additional weeks. 3. Captopril reduced blood pressure by 12.2 ± 0.8/9.4 ± 0.4 mmHg at 7 weeks (n = 323) and captopril plus placebo by 10.3 ± 1.9/10.2 ± 0.9 at 14 weeks (n = 83); placebo by 20 ± 1.7/3.4 ± 0.8 (n = 76); captopril plus hydrochlorothiazide by 24.4 ± 1.1/16.2 ± 0.6 (n = 173). The effect of low-dose captopril was similar to that of a high dose. The effect of twice-daily captopril appeared to be equal to that of thrice-daily treatment but monitoring studies are needed to confirm this. 4. Only 15 out of 384 (3.9%) of patients were dropped from the study because of adverse effects. 5. Low-dose captopril may be useful in patients with mild to moderate hypertension.

Effects of captopril on urinary excretion of prostaglandins and electrolytes in spontaneously hypertensive rats

Captopril was administered to spontaneously hypertensive rats (SHR) and the acute and long-term effects on the urinary excretion of Na, K, prostaglandin (PG) E 2 and PGF 2α were studied. Captopril (30 mg and 100 mg/kg, p.o.) increased urine volume, urinary Na and K excretion on the 1st and 2nd days of its administration. The urinary K/Na ratio was decreased in the captopril-treated groups on the 1st to 3rd day. Urinary PGE 2 excretion in the captopril 100 mg/kg group was significantly increased compared to that in the control group (210.6±31.4 vs. control 123.2±8.4 ng/day) on the 1st day of captopril administration. A slight but significant increase in urinary PGF 2α excretion was also seen in the captopril 100 mg/kg group (105.2±9.8 vs. control 75.8±2.1 ng/day). But PG excretion declined during prolonged treatment and these were no significant difference between the control and captopril-treated groups on the 3rd and 6th week. These data suggest that captopril increases renal PG only as an acute phase and that the increase of PG at least partly accounts for natriuretic effects of the agent.

Effect of the angiotensin-converting enzyme inhibitor, captopril, on development of renal hypertension in rats.

42 female rats (230–260 g) made hypertensive by bilateral renal encapsulation with latex envelopes were divided into three equal groups. Two groups were administered the angiotensin-converting enzyme inhibitor captopril (SQ 14,225) in drinking water at a concentration sufficient to yield a dose of 25 and 50 mg/kg/day, respectively. The third group was untreated. A fourth group (14 rats) served as a normotensive control group. Systolic blood pressures and body weights were measured weekly during a 4-week control and an 8-week experimental period. Both doses prevented the elevation of blood pressure to the level of the untreated hypertensive controls. Blood pressure of the group receiving the higher dose of captopril was within the range of that of the normotensive control group by the end of the experiment while that of the group receiving the lower dose was between the blood pressures of untreated hypertensive and normotensive controls. Renal encapsulation resulted in failure of the rats to grow normally. Administration of captopril at either dose had no additional effect on body weight. To test whether inhibition of the angiotensin-converting enzyme occurred at the doses of captopril used, angiotensin I (200 µg/kg s.c.) and bradykinin (200 µg/kg s.c.) were administered separately and their effects on water intakes of control and captopril-treated groups tested. Captopril inhibited the drinking response to angiotensin I while increasing it in response to bradykinin. The pressor response following intravenous administration of 1.25 µg angiotensin I/kg to anesthetized rats was also studied. The groups treated with captopril had a significantly reduced response to angiotensin I compared with those of either normotensive or hypertensive groups. The results of the three tests suggest that inhibition of the angiotensin-converting enzyme occurred at both doses of captopril, with the higher dose inducing a somewhat greater inhibition. At autopsy, heart weight of the group receiving the higher dose of captopril was significantly less than that of the untreated hypertensive group, but significantly greater than that of the normotensive group. These results also suggest that captopril, at the doses used, provided significant protection against elevation of blood pressure in renal hypertensive rats.