Influence of extracellular Ca2+ on the modulation of alpha-adrenergic-induced contractions in rat aorta.
1. Rat thoracic aortic rings with and without endothelium incubated in a Ca2(+)-free solution showed a significant reduction of the maximal contraction (E max) induced by norepinephrine (NE) and phenylephrine (Ph), while the contraction induced by a 70 mM KCl depolarizing solution was completely abolished. 2. After Ca2+ removal, pD2 values (-log ED50) for NE and Ph were significantly reduced only in vessels without endothelium. 3. Under control conditions, clonidine (C) induced a contraction only in vessels without endothelium; this response was completely abolished by Ca2+ removal and by nifedipine (10(-8) M). 4. Pre-incubation with nifedipine (10(-8) M) produced an effect similar, although less pronounced, than the removal of Ca2+ in vessels with and without endothelium. 5. Nevertheless, aortic rings with intact endothelium showed a greater reduction of E max than rings without endothelium, suggesting that the endothelial layer may act in synergism with calcium channel blockers to inhibit the contractions induced by alpha-adrenergic agonists. 6. The modulation exerted by the endothelium on alpha 1- and alpha 2-adrenergic-induced contractions in rat aortic rings seems to depend both on extracellular Ca2+ concentration and on the release and action of endothelial relaxing factor(s).
Vinet
R
R
Department of Pharmaceutical Sciences, University of Valparaiso, Chile.
Brieva
C
C
Pinardi
G
G
Penna
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004730:Endothelium, Vascular; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009543:Nifedipine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine