INVOLVEMENT OF CA2-ADRENOCEPTORS IN ENDOTHELIN-1 EFFECTS ON THE TONE AND ELECTRICALLY-EVOKED CONTRACTIONS OF RABBIT EAR CENTRAL ARTERY( ANDALPHA(1))

Endothelin-1 (ET-1) is a neuropeptide strongly involved in the functio ns of the the cardiovascular system. The aim of the present study was to reveal the role of alpha(1)-adrenoceptors and of Ca2+ in the effect s of ET-1 on blood vessels. Preparations isolated from the proximal pa rt 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 org an bath with Krebs-Henseleit solution aerated with 95% O-2 and 5% CO2. The preparations were perfused at a rate of 3.0 ml/min maintaining th e arterial pressure in the range of 40-60 HPa and were allowed a 120-m in adaptation at 37.5 degrees C. Contractions were induced by low-freq uency electrical stimulation (ES) and the effects of ET-1 (applied int ralumenally or extralumenally) on the arterial tone and on the ES-evok ed 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 con centrations of 1 x 10(-8)M-1 x 10(-7)M ET-1 slightly increased arteria l tone and slightly enhanced the ES contractions. ET-1, in concentrati ons higher than 1 x 10(-7)M, sharply, strongly and long-lastingly incr eased the smooth muscle tone and slightly enhanced the ES contractions . A 100 mu M bolus injection with ET-1 (1 x 10(-9)M-1 x 10(-8)M) resul ted in potentiation of the ES contractions and the arterial tone was n ot markedly affected. 100 mu M 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 c ontractions. Perfusion with 1 x 10(-8)M ET-1 resulted in a 3-fold incr ease 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 effe cts of 1 x 10(-12)M-1 x 10(-9)M ET-1 and the effect of 1 x 10(-8)MET-1 on REA tone was even enhanced by PRZ. Under the same conditions 1 x 1 0(-6)M punarazine (FLU) inhibited the ES-induced contractions of the i solated preparations and decreased their tone. FLU reduced the contrac tile effects of ET-1 (1 x 10(-12)M-1 x 10(-8)M). Applied extralumenall y 1 x 10(-6)M (FLU) also decreased ET-1 effects on REA. The results ob tained strongly support the assumption that alpha(1)-receptors and Ca2 + are involved in ET-1 contractile effects on blood vessels smooth mus cles.