Hypotensive Effect Of Captopril Research Articles

Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration

The role of the gut microbiota in various metabolic diseases has been widely studied. This study aims to test the hypothesis that gut microbiota dysbiosis is associated with DOCA-salt-induced hypertension, while captopril, an antihypertensive drug, is able to rebalance the gut microbiota alterations caused by hypertension. Treatment with captopril resulted in an approximate 32 mmHg reduction in systolic blood pressure (162.57 vs. 194.61 mmHg) in DOCA-salt-induced hypertensive rats, although it was significantly higher than that in SHAM rats (136.10 mmHg). Moreover, the nitric oxide (NO) level was significantly increased (20.60 vs. 6.42 µM) while the angiotensin II (Ang II) content (42.40 vs. 59.47 pg/ml) was attenuated nonsignificantly by captopril treatment in comparison to those of DOCA-salt-induced hypertensive rats. The introduction of captopril significantly decreased the levels of tumor necrosis factor-α (TNF-ɑ) and interleukin-6 (IL-6). Hypertrophy and fibrosis in kidneys and hearts were also significantly attenuated by captopril. Furthermore, gut microbiota dysbiosis was observed in DOCA-salt-induced hypertensive rats. The abundances of several phyla and genera, including Proteobacteria, Cyanobacteria, Escherichia-Shigella, Eubacterium nodatum and Ruminococcus, were higher in DOCA-salt-induced hypertensive rats than in SHAM rats, while these changes were reversed by captopril treatment. Of particular interest, the genera Bifidobacterium and Akkermansia, reported as beneficial bacteria in the gut, were abundant in only hypertensive rats treated with captopril. These results provide evidence that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt-induced hypertensive rats, suggesting that the alteration of the gut flora by captopril may contribute to the hypotensive effect of this drug.

Possible impact of nitric oxide on the antihypertensive effect of captopril and zaprinast.

The interaction between the renin-angiotensin system and nitric oxide (NO) is undeniable, but its nature is not fully known. This study investigated the contribution of NO to the acute hypotensive effect of captopril in conscious normotensive rats and the effect on blood pressure of dual administration of captopril and the phosphodiesterase-5 inhibitor zaprinast. In two separate experiments, rats were pretreated with the NO inhibitor L-arginine methyl ester (L-NAME) and with the NO enhancer zaprinast. Pretreatment with L-NAME attenuated and pretreatment with zaprinast potentiated the hypotensive effect of captopril. The hypotensive effect of captoril was not associated with a significant change in the plasma level of cyclic guanosine monophosphate (cGMP). These findings suggest that NO contributes to the blood pressure-lowering effect of captopril. The inability of captopril to alter plasma cGMP levels is not consistent with this view, however, and leads to the conclusion that NO contributes to the acute hypotensive effect of captopril, although the mechanism is not fully understood. Zaprinast potentiates the hypotensive effect of captopril, and an adjustment in dose should be considered when this combination is administered.

Hypotensive effects of captopril on physical properties of the arterial system in young and adult rats.

We determined the acute effects of the angiotension converting enzyme inhibitor captopril on the arterial mechanics in rats at different ages, based on the exponentially tapered T-tube model. Male Wistar-Kyoto rats aged 4 and 12 months were individually referred to as young (n = 8) and adult rats (n = 8) and were anesthetized and thoractomized. The pulsatile aortic pressure and flow signals before and after the administration of captopril (20 mg/kg, i.p.) were measured by a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. In each age group, captopril showed little change in basal heart rate as well as cardiac output. However, captopril produced a drop of 15% in mean aortic pressure in young and a fall of 12% in adult rats. In addition. captopril reduced total peripheral resistance by 21% in young and by 23% in adult animals. As for the pulsatile nature of the arterial system, captopril had increased wave transit time of the lower body circulation of 10% in young and of 12% in adult rats. By contrast, captopril reduced wave reflection factor by 22% in young and by 25% in adult animals. In conclusion, the converting enzyme inhibitor captopril has a stiffness-decreasing effect on Windkessel vessels and a dilated effect on resistance arterioles in either young or adult rats. No age dependence of vascular response and reflex tachycardia to captopril has been found in rats between 4 and 12 months.

Role of Nitric Oxide in Responses to Renin-Angiotensin System Inhibition in Sodium-Depleted Guinea Pig and Rat

Previous reports have suggested that NO is an important mediator of the antihypertensive effects of renin-angiotensin system (RAS) inhibition. We examined the effects of the NO synthase inhibitor L-NNA on the hypotensive effects of captopril, the Ang II antagonist EXP 3174, or the renin inhibitor terlakiren. In sodium-depleted guinea pigs (GPs), L-NNA (3 mg/kg) increased MAP by 15–21% for at least 5 hours. L-NNA partially blocked the hypotensive effects of captopril (1 mg/kg, iv), but not those of EXP 3174 (1 mg/kg, iv) or terlakiren (3 mgkg). In sodium-depleted rats, 10 mg/kg L-NNA (iv) increased MAP by 16–22%, and partially or fully blocked the hypotensive effect of EXP 3174 (1 mg/kg, iv) or captopril (3 mgkg, iv), respectively. Thus, in contrast to the rat, NO in GPs appears to participate only in the hypotensive action of ACE inhibition and does not appear to be strongly involved in the hypotensive action of A11 antagonism or renin inhibition. The involvement of NO in the hypotensive effects of RAS antagonists other than ACE inhibitors may be species-dependent

Captopril-induced hypotension is inhibited by the bradykinin blocker HOE-140 in Na(+)-depleted marmosets.

Inhibition of angiotensin-converting enzyme (ACE) inhibits formation of angiotensin II and, by inhibition of kinin metabolism, may also increase vascular bradykinin. The present experiments were done in sodium-depleted, conscious, unrestrained marmosets (n = 5-11) to examine the contribution of bradykinin to ACE inhibitor-induced hypotension. Aortic blood pressure and heart rate (HR) were monitored via telemetry. After sodium depletion (low-sodium diet and furosemide), captopril (1 mg/kg po) caused a significant (P < 0.05) decrease in mean arterial blood pressure (MABP) (-34 +/- 3 mmHg, maximally, from 79 +/- 2 mmHg) but no change in HR compared with vehicle treatment. The bradykinin receptor antagonist HOE-140 (1 mg/kg sc) significantly inhibited the hypotensive response to captopril and caused marked tachycardia (+133 +/- 14 beats/min from 214 +/- 8 beats/min). HOE-140 (1 mg/kg sc) followed by vehicle administration had no effect on MABP but increased HR similarly. The hypotensive response to captopril was inhibited by HOE-140 regardless of the order of administration or the route of captopril administration (by mouth vs. subcutaneously). The hypotensive response to a renin inhibitor, A-72517 (3 mg/kg sc), was not inhibited by prior HOE-140 administration despite a similar HOE-140-induced tachycardia. These data suggest that the hypotensive effect of captopril in sodium-depleted, conscious marmosets is dependent on functional bradykinin B2 receptors. Also, blockade of B2 receptors uncovers marked tachycardia in this model, suggesting a tonic effect of bradykinin on control of HR in marmosets.

Facilitation by procaterol, a β‐adrenoceptor agonist, of noradrenaline release in the pithed rat independently of angiotensin II formation

1. The effects of the beta 2-adrenoceptor agonist, procaterol, on sympathetic neuroeffector transmission were studied in the pithed adrenal demedullated rat to determine if generation of angiotensin II was involved in its effect. Pressor responses were elicited by either electrical stimulation (20 V, 2 Hz) of the entire spinal sympathetic outflow or methoxamine (0.1 mg kg-1, i.v.). 2. Sodium nitroprusside (3 and 5 micrograms kg-1 min-1, i.v.) produced hypotension and the pressor responses to both sympathetic nerve stimulation and methoxamine were reduced. This indicates that decreasing blood pressure in pithed rats reduces pressor responses. Procaterol (10 and 30 ng kg-1 min-1, i.v.) also produced hypotension but did not alter pressor responses to sympathetic nerve stimulation. Nevertheless, procaterol (10 and 30 ng kg-1 min-1, i.v.) did reduce pressor responses to to methoxamine. Together these results suggest that procaterol may have enhanced sympathetic neurotransmitter release. This was confirmed in another series of experiments where procaterol (30 ng kg-1 min-1, i.v.) increased plasma noradrenaline levels during sympathetic nerve stimulation. 3. Captopril (5 mg kg-1, i.v.) produced hypotension and as expected reduced pressor responses to sympathetic nerve stimulation. When the hypotensive effect of captopril was abolished by concomitant vasopressin infusion (1.5-4.5 i mu kg-1 min-1, i.v.), pressor responses to sympathetic nerve stimulation were restored to pre-captopril levels. In this situation procaterol (10 and 30 ng kg-' min', i.v.) reduced basal blood pressure and did not alter pressor responses to sympathetic nerve stimulation whereas the pressor responses were reduced by an equihypotensive infusion of sodium nitroprusside (3 and 5 jig kg-' min' , i.v.). The lack of reduction of pressor responses after procaterol in the presence of captopril is indirect evidence that procaterol may have enhanced noradrenaline release independently of angiotensin II.4. In another series of experiments, plasma noradrenaline levels elicited by sympathetic nerve stimulation were not altered by captopril (5 mg kg', i.v.). In the presence of captopril (5 mg kg-', i.v.),procaterol (30 ng kg- min-1, i.v.) no longer enhanced plasma noradrenaline levels during sympathetic nerve stimulation. However, since the dose of captopril is well above that required to block angiotens in converting enzyme (ACE) the effect may be non-specific. Therefore, the selective AT, receptor antagonist, losartan (10mgkg'1, i.v.), was also used. Losartan (10mgkg'1, i.v.) did not alter plasma noradrenaline levels during sympathetic nerve stimulation, and in the presence of losartan procaterol(30 ng kg-I min-', i.v.) enhanced plasma noradrenaline levels during sympathetic nerve stimulation. This result further suggests that 1-adrenoceptor facilitation of noradrenaline release from sympathetic nerves in the pithed rat occurs by a mechanism independent of angiotensin II generation.

The hypotensive action of captopril and enalapril is not prostacyclin dependent

Angiotensin converting enzyme inhibitors have been proposed to have a prostaglandin-dependent component to their hypotensive action. The aim of this study was to assess whether the structurally dissimilar angiotensin converting enzyme inhibitors captopril and enalapril stimulate the synthesis of prostacyclin, whether their hypotensive action is blunted by indomethacin, and whether these biochemical or physiologic parameters differ for the two drugs, in white subjects with essential hypertension. Twelve patients were enrolled and 11 finished the study. The study consisted of a double blind, randomized, double-crossover design. All patients received either placebo or 50 mg indomethacin twice a day for 3 weeks; after 1 week of placebo or indomethacin either 50 mg captopril or 10 mg enalapril twice a day was added and continued for 2 weeks. Each patient received every possible combination. Neither captopril nor enalapril stimulated prostacyclin production as determined by measurement of the urinary excretion rate of its main enzymatic metabolite, 2,3-dinor-6-keto-prostaglandin-F1 alpha. Although indomethacin reduced the urinary excretion of the enzymatic metabolite of prostacyclin by more than 50%, it did not influence the hypotensive effect of captopril or enalapril. We conclude that neither captopril nor enalapril have a significant prostacyclin-dependent component to their hypotensive action.

A Clinical Study on the Hypotensive Effect of Captopril(Capril®)

A Clinical Study on the Hypotensive Effect of Captopril(Capril®)

A Clinical Study on the Hypotensive Effect of Captopril

A Clinical Study on the Hypotensive Effect of Captopril

Kinetic studies of the pharmacologic response to captopril in rats. II. Hypotensive effect and plasma angiotensin converting enzyme activity.

The effect of captopril on the mean arterial blood pressure was studied in rats. Two different disease-state rats, namely the sodium-deficient rat (SDR) and the two-kidney-one-clip Goldblatt hypertensive rat (GHR), as well as normotensive rats (NR), were used. After i.v. bolus administration of captopril to each rat, the time course of plasma angiotensin converting enzyme (ACE) activity and mean arterial blood pressure were determined. In a different experiment, the effect of captopril on the plasma ACE activity in vitro was determined. Captopril inhibited the plasma ACE activity in a concentration-dependent manner and the relationship between concentration of captopril and inhibition of plasma ACE activity in vitro was reasonably described by a Langmuir-type equation. Then, plasma concentrations of captopril after i.v. administration were estimated by means of this equation. The estimated plasma concentration of captopril followed a double exponential equation. From the data obtained, a kinetic model including the renin-angiotensin system and pharmacokinetics of captopril was constructed under the following assumptions; (1) the hypotensive effect of captopril is solely attributable to the reduction of angiotensin II level in the body, (2) the production rate of angiotensin II is proportional to the total ACE activity and (3) plasma ACE activity reflects the total ACE activity in the body. Then, the effect of captopril on the mean arterial blood pressure in each type of rat was calculated. The results indicated that the hypotensive effect of captopril in NR was reasonably described by the model. However, the hypotensive effect of captopril in both GHR and SDR could not be well described by the model.(ABSTRACT TRUNCATED AT 250 WORDS)

The hypotensive effect of captopril is not mediated by renal medullary lipids.

The role of renomedullary lipids in the hypotensive effect of captopril was studied in spontaneously hypertensive rats, one-kidney, one clip hypertensive rats and two-kidney, one clip hypertensive rats using inhibitors of acetyl glyceryl ether phosphorylcholine and prostaglandins, and chemical medullectomy. Our experiments indicate that it is unlikely that renomedullary lipids contribute to the hypotensive action of captopril.

Clinical Trial on the Hypotensive Effect of Captopril

Clinical Trial on the Hypotensive Effect of Captopril

Acute effects of captopril on the baroreflex of normotensive and spontaneously hypertensive rats.

When captopril was injected intravenously in urethane anesthetized rats, a hypotensive effect accompanied by bradycardia was obtained, while an intravenous (i.v.) injection of prostaglandin I2 (PGI2), which induced hypotension of the same magnitude as the hypotensive effect obtained with captopril, caused a marked tachycardia. Simultaneously, sympathetic nerve activity recorded from abdominal sympathetic nerves was unchanged following injection of captopril, while it was significantly increased during hypotension induced by PGI2. The bradycardia, but not the hypotensive effects induced by captopril was abolished by i.v. pretreatment with atropine. Intracisternal injection of a small dose of captopril inhibited reflex tachycardia during hypotension induced by PGI2 and prolonged the hypotensive effect, while intravenous administration of this dose did not inhibit the reflex tachycardia induced by PGI2. In spontaneously hypertensive rats (SHR), the hypotensive effect of captopril was increased partly, however, the accompanying bradycardia was significantly reduced. These findings suggest that captopril inhibits the baroreflex and centrally activates the cardiac vagal nerve. Moreover in SHR, the effect of captopril on cardiac vagal activity was disturbed.

Effect of DOCA-salt on Angiotensin Dependency and Surgical Reversal of Hypertension in Two-kidney, One Clip Renal Hypertensive Rats

The development of hypertension in two-kidney, one clip renal hypertensive rats (2K, 1C RHR) was not altered by treatment with DOCA and saline solution as drinking fluid for two months of observation. However, the administration of DOCA and salt suppressed plasma renin activity (PRA), the renal renin content (RRC) of the clipped kidney and the response to a single oral dose of captopril (10 mg/kg). The weight of the contralateral kidney was increased by the administration of DOCA-salt, while that of the ischaemic kidney was not changed. The withdrawal of DOCA-salt treatment restored the PRA and the effects of captopril to a similar degree to the non-treated group. The acute hypotensive effects of captopril were reduced on the 10th week compared with the 7th week after renal arterial constriction in 2K, 1C RHR. The fall in blood pressure induced by captopril significantly correlated with the initial PRA both in the 7th and 10th week after clipping. There was a significant correlation between PRA and RRC of the clipped kidney. Rats previously treated with DOC-salt had either removal of the contralateral kidney with removal of the clip from the ischaemic kidney, or removal of the ischaemic kidney. Blood pressure fell to normal levels in the unclipped group and in the nephrectomy group, but the fall in the latter group was transient and within two weeks had risen to significantly higher levels than in the unclipped group. It is concluded that structural vascular change following DOC-salt hypertension is insufficient to cause persisting hypertension except when it occurs in the renal circulation.

What stimulates the renin-angiotensin system in rats with two-kidney renal hypertension?

1. Blood pressure, the hypotensive effect of captopril, plasma renin activity, renal renin content and kidney weight were measured in the two-kidney—one-clip model, the one-kidney—one-clip model and the two-kidney—one-clip model with the ureter of the contralateral kidney ligated in rats. The ureteric ligation was performed to abolish urinary excretion from the contralateral kidney in the two-kidney—one-clip model. 2. The development of hypertension after renal artery constriction was earlier and greater in the one-kidney—one-clip model and the two-kidney—one-clip model with ureter of the contralateral kidney ligated than in the two-kidney—one-clip model. A single oral dose of captopril produced a greater fall in blood pressure in both the two-kidney models than in the one-kidney—one-clip group. 3. Plasma renin activity and renal renin content of the clipped kidney were higher in the two-kidney model rats, whether or not the ureter had been ligated, than in the one-kidney—one-clip model animals, although more than half the rats from the two-kidney model had normal values. There was a significant correlation between plasma renin activity and the response to captopril in all groups, whereas in none of the three groups was the correlation between plasma renin activity and blood pressure significant. 4. The clipped kidney had a higher renin content than did the contralateral kidney, and the weight of the ischaemic kidney was decreased compared with the contralateral kidney whether it was untouched or had its ureter ligated. The weight of the clipped kidney was in the order one-kidney—one-clip model &amp;gt; two-kidney—one-clip model with ureter of the contralateral kidney ligated &amp;gt; two-kidney—one-clip model. 5. It was concluded that the renin-angiotensin system was stimulated to the similar degree in some animals for the two-kidney—one-clip models, whether or not the ureter of the contralateral kidney had been ligated, compared with the one-kidney—one-clip animals. This finding suggests that the contralateral kidney can stimulate renin secretion and synthesis in the clipped kidney independently of Na+ excretion.

First dose hypotensive effect of captopril

First dose hypotensive effect of captopril

Hypotensive effect of captopril in hypertensive patients with collagen disease

Hypotensive effect of captopril in hypertensive patients with collagen disease

Acute hypotensive and renin-stimulating actions of captopril before and during treatment with a beta-blocking drug

There is no general agreement on the relation between the hypotensive effect of captopril and the pretreatment plasma renin levels of hypertensive patients. To determine whether the hypotensive effect of captopril was directly related to plasma renin, the angiotensin-converting enzyme inhibitor was administered acutely to 10 essential hypertensive patients with normal or suppressed plasma renin activity before and after inhibition of renin secretion with propranolol. Captopril was equally effective in reducing blood pressure both when administered alone (25 mg: −29 −17 ; 50 mg: −37 −23 mm Hg) and after chronic treatment with propranolol (25 mg: −33 −20 ; 50 mg: sol−30 −20 mm Hg). The increase in renin induced by captopril was not decreased by propranolol therapy. The persistence of the hypotensive effect of captopril after renin suppression by propranolol suggests that this drug has some blood pressure decreasing properties independent of plasma renin.

Hypotensive Effect of Captopril in SHR

Hypotensive Effect of Captopril in SHR

Evaluation of hypotensive mechanisms of captopril in addition to its inhibition of the converting enzyme in spontaneously hypertensive rats.

In spontaneoulsy hypertensive rats (SHR), the hypotensive effect of captopril (30 mg/kg/day per os for 4 days), which inhibits the converting enzyme when given orally was significantly potentiated rather than suppressed by aprotonin (100,000 KIU/day s.c. for 7 days), but was not affected by indomethacin. These findings suggest that neither the kallikrein-kinin system nor the prostaglandin system is involved in any of the hypotensive actions of captopril in SHR other than the inhibition of the converting enzyme.