Estrogen-induced relaxation of the rat tail artery is attenuated in rats with pulmonary hypertension.
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.
Kocić
Ivan
I
Departament of Pharmacology, Medical University of Gdańsk, Debowa 23, PL 80-204 Gdańsk, Poland. ikocic@amg.gda.pl
Szczepańska
Renata
R
Wapniarska
Iga
I
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D054086:KATP Channels / Q000187:drug effects; D008297:Male; D016686:Monocrotaline; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011042:Poisons; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D054086:KATP Channels; D011042:Poisons; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D004958:Estradiol; D016686:Monocrotaline