Kinins, nitric oxide, and the hypotensive effect of captopril and ramiprilat in hypertension.

Abstract

We investigated the role of kinins in the acute depressor effect of captopril and ramipriiat in spontaneously hypertensive rats. Since the vasodepressor action of kinins may be linked to the generation of prostaglandins and endothelium-derived relaxing factors, we also investigated the role of prostaglandins and nitric oxide in the blood pressure reduction caused by angiotensin converting enzyme inhibitors. To this end, we contrasted the hypotensive effects of captopril ( factors and vasodepressor prostaglandins. 6 ' 7 Contribution of kinins to the acute antihypertensive effect of ACE inhibitors is evidenced by reports that such an effect is poorly expressed in hypertensive rats deficient in kininogen and kinins (Brown Norway rats with two kidney, one-clip hypertension) 8 and is attenuated by the administration of kinin antibodies 9 or kinin antagonists in models of renin-dependent hypertension in standard strains of rats.

Perindopril changes the mesenteric pressure profile of conscious hypertensive and normotensive rats.

“…The comparatively slow drop in blood pressure after bolus injection of perindopril is similar to the finding of Cachofeiro et al, 14 who observed that an intravenous bolus injection of ramiprilat (2 mg/kg) caused a fall in MBP that took 30 minutes to reach a maximum. The work of Richer et al 15 shows that 180 minutes after bolus injections of perindopril, the forearm resistance is reduced.…”

Involvement of nitric oxide, but not prostaglandins, in the vascular sympathoinhibitory effects of losartan in the pithed spontaneously hypertensive rat

“…Recent studies have suggested that endothelial AII AT,-receptor blockade per se enhances NO production (Sudhir et al, 1993) and upregulates endothelial NO synthase in elastic arteries (Holtz et al, 1994). Moreover, losartan as a vasodilator increases regional blood flows which through augmented shear stress may enhance NO release (Cachofeiro et al, 1992). Finally, endothelial dysfunction has been shown to be associated with hypertension (Liischer & Vanhoutte, 1986) and the possibility cannot be excluded that an 8-day treatment with losartan may have partly restored in our SHRs their impaired ability to produce NO in response to endothelium-dependent vasodilators.…”

“…Cachofeiro et al (1992) have shown in the SHR that the acute reduction in blood pressure induced by the drug is reduced by approximately 60% when the animals are pretreated with L-NMMA. Similar findings have been reported by others (Kumagai et al, 1993;Pollock et al, 1993;Sudhir et al, 1993) and in our study, L-NAME raised blood pressure and vascular resistances in losartan-treated animals.…”

Effects of Cilazapril on Endothelial Function and Pulmonary Hypertension in Patients with Congestive Heart Failure.

“…24) Many trials including the Cooperative North Scandinavian Enalapril Survival Study, (CONCENSUS), the Studies of Left Ventricular Dysfunction (SOLVD), and the Survival and Ventricular Enlargment (SAVE) trial have demonstrated the ability of ACE inhibitors to improve hemodynamic parameters and reduce mortality within a wide range of heart failure. [25][26][27] The current study demonstrated that 3 months of cilazapril therapy improves impaired endothelium-Vol 43 No 6 dependent vasodilatation in the brachial circulation of patients with atherosclerotic diseases and heart failure. During the past two decades, it has been well established that vascular endothelium plays a pivotal role in maintaining vascular tone.…”

“…The position was maintained throughout the test, and a similar position was used in the subsequent studies. Baseline images and Vol 43 No 6 pulsed Doppler flow velocity measurements were taken (Figure). A pneumatic tourniquet was then placed proximally on the forearm and inflated to 250 mmHg of pressure for 5 minutes and rapidly deflated resulting in reactive hyperemia.…”