Pharmacological evaluation of the angiotensin, kinin, and neurokinin receptors on the rabbit vena cava.
Angiotensin II, bradykinin, and substance P are powerful vasoconstrictors of venous smooth muscle. In this report, we have characterized the receptors and the cellular mechanisms of these vasoactive peptides on a new isolated smooth muscle preparation, the rabbit vena cava. Receptors were characterized using agonists and antagonists and were found to be of the AT, B2, and NK-1 types. The myotropic responses of the vein to KCl was completely abolished in calcium-free medium; in the presence of nicardipine, nifedipine, and verapamil, three calcium channel antagonists; and of trifluoperazine, a calmodulin antagonist. AT II-, BK-, and SP-induced responses were slightly attenuated in calcium-free medium and in the presence of nifedipine and trifluoperazine. Pinacidil inhibited the contractile response of KCl and the three peptides while lidocaine was active against KCl only. Staurosporine and cholera toxin strongly inhibited the contractile responses of the vein to AT II, BK, SP, and KCl, probably by a nonspecific effect. It is concluded that AT II-, BK-, and SP-induced contractions of the rabbit vena cava are mediated by specific receptors and in part by an influx of extracellular Ca2+ through dihydropyridine-insensitive channels. Opening of K+ channels and inhibition of the Ca(2+)-calmodulin complex appear to interfere with the smooth muscle response to the peptides.
Nantel
F
F
Department of Pharmacology, Medical School, University of Sherbrooke, Quebec, Canada.
Rouissi
N
N
Rhaleb
N E
NE
Jukic
D
D
Regoli
D
D
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000187:drug effects*; D018002:Receptors, Bradykinin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D014682:Vena Cava, Inferior / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015221:Potassium Channels; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D015222:Sodium Channels; D000804:Angiotensin II; D013373:Substance P; D001920:Bradykinin; D002118:Calcium