RESUMO
The mechanisms involved in the effects of estrogen on arterial smooth muscle contractility are very complex and not fully clarified. Therefore, the aim of this paper was to examine the mechanisms of estrogen-induced relaxation of the rat tail artery and, specifically, how pulmonary hypertension affects this action. We used male rats and performed experiments on isolated tail arteries in a control group and a group with pulmonary hypertension (PAH) induced by monocrotaline (60 mg/kg b.w. ip). The pD2 value (-log EC50) of phenylephrine significantly decreased in the presence of 20 microM of 17beta-estradiol (5.4 +/- 0.13 vs. 4.9 +/- 0.12, p < 0.05, n = 6). Estrogen-induced relaxation of a phenylephrine-precontracted tail artery has two components: endothelium-dependent (ED) and endothelium-independent (EI). The estrogen effect was independent of ATP-sensitive K+ channels, vasoactive prostanoids and nitric oxide. PAH augmented the maximal effect of phenylephrine on the tail artery contractility but did not affect estrogen-induced ED-relaxation. However, the EI component of relaxation induced by estrogen was completely abolished in tail arteries obtained from animals with pulmonary hypertension. Pulmonary hypertension affects the sensitivity of the rat tail artery to phenylephrine and estrogen, leading to impairment of EI mechanisms of relaxation. Further experiments are required to elucidate the molecular mechanisms of this phenomenon.
Assuntos
Artérias/efeitos dos fármacos , Estradiol/farmacologia , Hipertensão Pulmonar/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Hipertensão Pulmonar/induzido quimicamente , Canais KATP/efeitos dos fármacos , Masculino , Monocrotalina , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/fisiologia , Fenilefrina/farmacologia , Venenos , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Cauda/irrigação sanguínea , Vasoconstritores/farmacologiaRESUMO
The effects of various statins on platelet aggregation in blood samples from normal and diabetic rabbits were measured. All of the statins used in our study inhibited platelet aggregation by about 20% at 1 microM. Our results show that diabetes increased the rate of platelet aggregation from 48 +/- 5% to 72 +/- 8%, however, statins inhibited the rate of platelet aggregation by about 60% (p < 0.01). The addition of leptin (125 ng/ml) to blood samples from healthy rabbits increased the aggregation rate to about 64%, but statins decreased this rate to about 26%. Our results indicate that diabetes increases the rate of platelet aggregation in rabbits and increases antiplatelet efficacy of statins due to interactions with leptin.