B(2)-receptor modulation of the reactivity to phenylephrine and angiotensin II in the carotid artery of normotensive rats after trandolapril treatment.
This study was designed to study the effects of angiotensin converting enzyme inhibitors (ACEI) following treatment with trandolapril (0.3 mg kg(-1) day(-1)) on carotid arterial responsiveness in normotensive Wistar rats. Carotid arteries were obtained from control or trandolapril-treated animals and mounted in an isolated organ bath. Reactivity to angiotensin II (Ang II), phenylephrine (Phe) and KCl was studied. Agonist concentration-response curves were constructed in either the absence or presence of the endothelium or after incubation with L-NAME (10(-6) M), HOE140 (10(-7) M) or indomethacin (10(-5) M). Trandolapril treatment decreased the Ang II and Phe potencies in carotid arteries, but did not affect the maximal response. The KCl responses (potency and Emax) were similar in both control and trandolapril-treated arteries. The absence of endothelium increased the response to both agonists in control and trandolapril-treated arteries; however, the inhibitory component from the endothelial layer of the Phe response was greater in trandolapril-treated animals than in control animals. The presence of L-NAME or HOE140 abolished the changes in the potency values of trandolapril-treated animals. The presence of indomethacin did not change the effect of trandolapril on the potency values of both agonists. We conclude that trandolapril treatment decreased the carotid arterial reactivity in normotensive rats and that this effect is endothelium-dependent. Furthermore, the involvement of B(2)-receptors and NO production, but not of prostaglandins, is suggested in this mechanism.
Accorsi-Mendonça
Daniela
D
Department of Pharmacology, School of Medicine of Ribeirão Preto, Brazil.
Corrêa
Fernando M A
FM
Oliveira
Ana M de
AM
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D004727:Endothelium / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D018343:Receptors, Adrenergic, beta-2; D000804:Angiotensin II; C052035:trandolapril; D010656:Phenylephrine; C065679:icatibant; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin