Release of endothelium-derived relaxing factor from resistance arteries in hypertension.
Aortic rings from SHR are reported to have a decreased relaxation response to the endothelium-dependent agent acetylcholine compared with rings from WKY rats. Thus, a reduced EDRF (nitric oxide) response could contribute to hypertension. We found that in mesenteric small resistance arteries (200 microns I.D.) taken from 5- to 50-week old rats and mounted in a Mulvany-Halpern myograph, that the concentration-response curves to acetylcholine were similar in range and sensitivity (EC50) in arteries from SHR and WKY rats at the same age. Similarly, in small resistance arteries from human buttock skin, the relaxation to acetylcholine was not different between vessels from normotensive volunteers (mean BP = 95.2 +/- 1.5 mm Hg) and patients with untreated essential hypertension (mean BP = 116.5 +/- 2.5 mm Hg). In rabbits with chronic renovascular hypertension (cellophane renal wrap), acetylcholine and adenosine infusions into the lower abdominal aorta caused falls in hindquarter resistance that were enhanced in range, but with no change in sensitivity compared with normotensive rabbits. In normotensive rabbits, nitric oxide synthase inhibition with N omega-nitro-L-arginine infusion caused a rise in blood pressure, fall in hindquarter conductance and blockade of the acetylcholine responses. These experiments suggest that at the level of resistance arteries in vivo and in vitro, a defect in the receptor-stimulated response to EDRF associated with hypertension could not be detected. Apparently, basal nitric oxide is important in resting vasodilator tone, but its role in chronic hypertension is still unclear.
Angus
J A
JA
Baker Medical Research Institute, Melbourne, Victoria, Australia.
Dyke
A C
AC
Jennings
G L
GL
Korner
P I
PI
Sudhir
K
K
Ward
J E
JE
Wright
C E
CE
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012867:Skin / Q000098:blood supply; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine