Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

Abstract

Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh) and bradykinin (BK) in nitric oxide (NO)-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR) with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg) or pentaerythritol tetranitrate (100 mg/kg), twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP) was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01) hypotensive response to ACh (1 and 10 µg, 87.9 ± 6.9 and 108.1 ± 5.1 vs 35.9 ± 4.7 and 64.0 ± 3.3 mmHg), and BK (100 µg, 106.7 ± 8.3 vs 53.3 ± 5.2 mmHg). SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 ± 3.6 vs 74.2 ± 8.6% in controls, P < 0.01). Iliac artery inner diameter also increased (680 ± 46 vs 828 ± 28 µm in controls, P < 0.01). Wall thickness, wall crosssection area, wall thickness/inner diameter ratio increased significantly (P < 0.01). No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NOdeficient hypertension.

The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats

“…NO-sensitive part cannot be fully responsible for the slightly improved endothelial-dependent relaxation, since acetylcholine and NO donors themselves are able to evoke relaxation of conduit arteries via additional regulatory mechanisms, such as hyperpolarization (Corriu et al 1996). Similarly, other regulatory mechanisms than NO may be engaged in blood pressure regulation, such as the hyperpolarizing factor which was proved to be important in the resistant part of arterial tree (Gerová et al 2004(Gerová et al , 2005Gerová and Kittová 2006). The morphological observation of iliac artery revealed that PETN administration had no effect on wall thickness, inner diameter, arterial wall mass, and wall thickness/inner diameter ratio.…”

Phytochemical and Toxicological Studies of an Extract of the Seeds of Picralima Nitida (Stapf) (Apocynaceae) and Its Pharmacological Effects on the Blood Pressure of Rabbit

“…The use of atropine, a competitive inhibitor of acetylcholine (Gerova et al, 2005;Hirota and McKay, 2006;de Azua et al 2012;Jain et al, 2012) reduced significantly the dose-dependent hypotension induced by Pn in rabbit. It indicates the presence of cholinomimetics substances in this crude extract.…”

“…Indeed, acetylcholine by binding to its muscarinic type receptors on heart, could cause, negative inotropic and chronotropic effects (Felder, 1995;Bois et al, 1999;Roffel et al, 2001;Racke and Matthiesen, 2004;Gerova et al, 2005;Hirota and McKay, 2006) and the vasorelaxation by releasing nitric oxide (NO) by endothelium (Furchgott and Zawadzki, 1980;Zapol et al, 1994;Ducrocq et al, 2001;Zhao et al, 2004;Lamblin et al, 2005;Collin and Levy, 2008;Jeanneret, Sanchez, Liaudet, 2011).…”

Effets pharmacodynamiques d’un extrait hydroalcoolique de Curcuma longa Linné (Zingiberaceae) sur le système cardiovasculaire, la respiration et l’activité mécanique intestinale de mammifères

“…La présence de substances anticalciques dans l'extrait hydroalcoolique de Cl est confirmée par le fait que, contrairement à l'ATR qui est un inhibiteur compétitif des récepteurs cholinergiques muscariniques [16,28], l'extrait de Cl inhibe les effets inotropes positifs induits par le BaCl 2 qui est un stimulateur de la motilité intestinale comparable au calcium [36].…”