Endothelial factors involved in the bradykinin-induced relaxation of the guinea-pig aorta.
Endothelial factors involved in the bradykinin (BK)-induced relaxation of the guinea-pig aorta were investigated using isolated aortic rings. In intact aortic rings, higher concentrations of BK (> or = 10(-7) M) produced contraction, possibly as a direct action on smooth muscle. This BK-induced contraction was enhanced either by Nw-nitro-L-arginine (NOLA), an inhibitor of the production of nitric oxide or by indomethacin (IND), an inhibitor of cyclooxygenase, but not by carbenoxolone (CX), a known inhibitor of gap junctions. In aortic rings contracted with noradrenaline, BK elicited a relaxation with two components; an initial fast relaxation followed by a gradually diminishing slow relaxation, both in an endothelium-dependent manner. The BK-induced relaxation was inhibited in a drug specific manner by either NOLA, IND or CX. NOLA either abolished the fast relaxation, or sometimes converted it into a contractile response. IND reduced the amplitude and duration of the relaxation, by inhibiting the fast relaxation and abolishing the following slow relaxation. CX reduced both components of the relaxation. In the presence of both NOLA and CX, the BK-induced relaxation was converted to a contractile response followed by an IND-sensitive slow relaxation. In the presence of NOLA and IND together, BK stimulation caused a contraction with no following relaxation. These results indicate that in aortic rings of the guinea-pig, BK stimulates endothelial cells to release nitric oxide and prostanoids that produce the fast and slow components of the relaxation respectively. The effects of CX suggest that the contribution of EDHF to the BK-induced relaxation is weak.
Kamei
M
M
Department of Physiology, Nagoya City University Medical School, Nagoya, Japan.
Yoneda
Y
Y
Suzuki
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology*; D002229:Carbenoxolone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D019335:Nitroarginine; D002229:Carbenoxolone; D001920:Bradykinin; D009638:Norepinephrine; D007213:Indomethacin