Involvement of Ca2+ and alpha 1-adrenoceptors in endothelin-1 effects on the tone and electrically evoked contractions of rabbit ear central artery
Todorov, S.; Petkov, O.; Nikolov, R.; Zamfirova, R.
Methods and Findings in Experimental and Clinical Pharmacology 17(6): 391-395
1995
ISSN/ISBN: 0379-0355 PMID: 8642900 Document Number: 445768
Endothelin-1 (ET-1) is a neuropeptide strongly involved in the functions of the cardiovascular system. The aim of the present study was to reveal the role of alpha1-adrenoceptors and of Ca2+ in the effects of ET-1 on blood vessels. Preparations isolated from the proximal part of ear central arteries (REA) of male Chinchilla rabbits were used. A 30-40 mm long segment, cannulated at both ends, was fixed in an organ bath with Krebs-Henseleit solutions aerated with 95% O2 and 5% CO2. The preparations were perfused at a rate of 3.0 ml/min maintaining the arterial pressure in the range of 40-60 HPa and were allowed a 120-min adaptation at 37.5 degree C. Contractions were induced by low-frequency electrical stimulation (ES) and the effects of ET-1 (applied intralumenally or extralumenally) on the arterial tone and on the Es-evoked contractions were studied. Extralumenal ET-1 (1 x 10(-12)M-1 x 10(-9)M) did not change the tone and ES evoked contractions of REA. In concentrations of 1 x 10(-8)M-1 x 10(-7)M ET-1 slightly increased arterial tone and moderately potentiated ES contractions. ET-1, in concentrations higher than 1 x 10(-7)M, sharply, strongly and long-lastingly increased the smooth muscle tone and slightly enhanced the ES contractions. A 100 microM bolus injection with ET-1 (1 x 10(-9)M-1 x 10(-8)M) resulted in potentiation of the ES contractions and the arterial tone was not markedly affected. 100 microM of 1 x 10(-7)M ET-1 increased more than 2-fold the tone of the segments and moderately reduced the ES-evoked contractions. A 30-min perfusion with ET-1 (1 x 10(-12)M-1 x 10(-9)M) strongly increased the arterial tone and completely abolished the ES contractions. Perfusion with 1 x 10(-8)M ET-1 resulted in a 3-fold increase of the tone of the isolated segments. A 30-min perfusion with 1 x 10(-6)M prazosin (PRZ) did not affect the arterial tone and prevented the ES-evoked contractions. PRZ markedly reduced the contractile effects of 1 x 10(-12)M-1 x 10(-9)M ET-1 and the effect of 1 x 10(-8)M ET-1 on REA tone was even enhanced by PRZ. Under the same conditions 1 x 10(-6)M flunarizine (FLU) inhibited the ES-induced contractions of the isolated preparations and decreased their tone. FLU reduced the contractile effects of ET-1 (1 x 10(-12)M-1 x 10(-8)M). Applied extralumentally 1 x 10(-6)M FLU also decreased EG-1 effects on REA. The results obtained strongly support the assumption that alpha1-receptors and Ca2+ are involved in ET-1 contractile effects on blood vessels smooth muscles.