Study of the in vivo and in vitro cardiovascular effects of a hydralazine‐like vasodilator agent (HPS‐10) in normotensive rats

Abstract

1 In this work, the cardiovascular e ects of HPS-10, a new vasodilator agent, were studied in rats. 2 In conscious normotensive rats, oral administration of HPS-10 (4 ± 9 mg kg 71 ) produced a doserelated and long-lasting fall in systolic arterial blood pressure (ED 30 of 5.32 mg kg 71 ), accompanied by an increase in heart rate (ED 30 of 8.43 mg kg 71 ). This tachycardia was totally inhibited by pretreatment with (+)-propranolol (10 mg kg 71 , p.o.). In rat isolated rubbed aorta, HPS-10 (0.1 ± 1 mM) non-competitively and with almost equal e ectiveness antagonized the contractions induced by NA, AII (in normal Krebs solution) and Ca 2+ (in depolarizing Ca 2+ -free high-K + 50 mM solution). In the experiments in Ca 2+ -free medium, HPS-10 (1 mM) considerably inhibited the contractions induced by NA, AII and ca eine in rat aorta. 5 Furthermore, in the studies with radioactive Ca 2+ , HPS-10 (1 mM) did not modify the basal uptake of 45 Ca 2+ but strongly decreased the in¯ux of 45 Ca 2+ induced by NA, AII and K + in rat aortic rings. 6 In rat isolated atria, HPS-10 (1 mM) produced a positive inotropic/negative chronotropic e ect. 7 HPS-10 (0.3 mM) signi®cantly inhibited the sustained and transient Ba 2+ inward current (I Ba ) recorded in whole-cell clamped rat aortic myocytes. 8 These results indicate that the non-selective vasorelaxant e ects of HPS-10 in rat aortic rings can be attributed to transmembrane Ca 2+ -antagonist activity and an intracellular action on smooth muscle cells. The direct vasodilator action of HPS-10 observed in rat isolated aorta may be responsible for the HPS-10 hypotensive activity in anaesthetized normotensive rats.

The Possible Implication oftrans-Resveratrol in the Cardioprotective Effects of Long-Term Moderate Wine Consumption

“…In our experiments, the rat aortic rings lacked spontaneous activity, as we have reported previously (Orallo, 1997). The resting tone was unaffected by DMSO (0.14-1.40 mM), atropine (10 M), yohimbine (1 M), and t-RESV (1-10 M) in endotheliumdenuded and/or intact rat aortic rings (n ϭ 5; p Ͼ 0.05; data not shown).…”

“…Vascular rings were prepared from the aortas of male Wistar rats weighing 250 to 300 g, essentially as described elsewhere (Orallo, 1997). In addition, contraction/relaxation studies were performed following the general method indicated in Orallo et al (1998).…”

Trans- andcis-resveratrol increase cytoplasmic calcium levels in A7r5 vascular smooth muscle cells

“…However, previous reports have shown that t-RESV directly relaxes rat aortic smooth muscle [8,9] (see Section 1). These discrepancies could be due to the following reasons: i) A different sensitivity to RESV of the A7r5 cloned cell line compared to the rat aortic smooth muscle cells (RASMCs) isolated from the medial layer of rat aorta (for detailed method of preparation, see [19]). In order to exclude or confirm this possibility, further investigations are currently being conducted in our laboratory to establish whether RESV also induces increases in [Ca 2+ ] i in RASMCs.…”

A Role of Ion Channels in the Endothelium-Independent Relaxation of Rat Mesenteric Artery Induced by Resveratrol

“…Vascular rings were prepared from the mesenteric arteries of male Wistar rats, body weight of 250 -300 g, essentially as described elsewhere (19). The studies reported in this work have been carried out in accordance with the European regulations on the protection of animals, the Declaration of Helsinki, and / or the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the United States National Institutes of Health.…”