Involvement of endothelium-derived factors in controlling the active tone of smooth muscle in aorta from hypertensive rats.
Control of the active tone by endothelium in aortae from various strains of spontaneously hypertensive rats was studied. The active tone was negligibly observed in endothelium-intact preparation. The application of N(G)-nitro-L-arginine (L-NNA, 10(-4) M) induced slowly developed active tone in the preparations from hypertensive rats but no active tone was induced in the preparation from normotensive Wistar Kyoto rats (WKY). The developed tension was stronger in preparations from rats with higher blood pressure as observed in endothelium denuded preparations. The developed active tone in the presence of L-NNA was greater than that observed in endothelium denuded preparations. The active tone was abolished by the removal of extracellular Ca2+ or by the application of Ca-antagonists. L-arginine counteracted the effects of L-NNA and depressed the developed active tone in the presence of the latter drug. The application of indomethacin (10(-5) M) depressed the active tone of the preparations from SHRSP by 25.5+/-5.2%. Increasing extracellular K+ concentration or application of tetraethylammonium (TEA) could not be used to observe the effect of endothelium-derived factors on the active tone, because of their strong contractile effect. Simultaneous application of apamin and charybdotoxin induced an elevation of tension which was often associated with spontaneous tension oscillation. It is concluded that the active tone, which is smooth muscle origin, is depressed by endothelium-derived nitric oxide (NO) strongly and potentiated by a product of arachidonic acid cascade through cyclooxygenase pathway. The involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressing effect of endothelium is thought to be small.
Sekiguchi
F
F
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan. fumiko@phar.kindai.ac.jp
Matsuda
K
K
Shimamura
K
K
Takeuchi
K
K
Sunano
S
S
D000818:Animals; D001011:Aorta; D001120:Arginine / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism*; D001794:Blood Pressure; D001835:Body Weight; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine