Arterial size determines the enhancement of contractile responses after suppression of endothelium-derived relaxing factor formation.
We studied the effect of endothelium-derived relaxing factor (EDRF) on norepinephrine-induced contractile responses and on the tissue guanosine-3',5'-phosphate (cGMP) concentration of isolated rabbit arteries with an increasing endothelium to smooth muscle cell ratio (aorta, femoral and mesenteric arteries). After suppression of EDRF formation (either by NG-nitro-L-arginine or, in mesenteric arteries, by saponin), contractions elicited by cumulative doses of norepinephrine were unaltered in aorta but were enhanced by 22.5% in femoral arteries and by 44.3% in mesenteric arteries (at the highest norepinephrine concentration). The cGMP concentration (pmol/mg protein) of unstimulated, endothelium-intact vessels decreased after suppression of EDRF formation from 1.09 +/- 0.24 to 0.74 +/- 0.28 in aortic, from 2.86 +/- 0.4 to 0.61 +/- 0.19 in femoral and from 6.3 +/- 0.9 to 0.7 +/- 0.15 in mesenteric arterial segments. The basal cGMP concentration did not differ in endothelium-denuded segments of these arteries, suggesting a similar basal activity of soluble guanylate cyclase (sGC). A higher sensitivity of sGC may have contributed to the higher cGMP concentration observed in the smaller arteries, since in the presence of sodium nitroprusside the cGMP concentration of endothelium-denuded segments increased 1.8-fold in aortic, 2.9-fold in femoral and 2.4-fold in mesenteric arterial segments. However, these differences in sGC activation cannot be solely responsible for the high basal cGMP concentration in endothelium-intact mesenteric arteries. The greater ratio of endothelium to smooth muscle cell layers in the smaller arteries might result in a higher EDRF concentration in the vascular wall and subsequently in a higher cGMP concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
University of Freiburg, Department of Medicine IV, Germany.
J
J
Galle
J
J
Bauersachs
E
E
Bassenge
R
R
Busse
D000818:Animals; D001011:Aorta / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000033:anatomy & histology* / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D012503:Saponins; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D009638:Norepinephrine