Hypertension in mice lacking the gene for endothelial nitric oxide synthase.
Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds. NO has been implicated in the regulation of blood pressure and regional blood flow, and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension. Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.
Huang
P L
PL
Cardiovascular Research Center, Medical Services, Massachusetts General Hospital, Boston 02129, USA.
Huang
Z
Z
Mashimo
H
H
Bloch
K D
KD
Moskowitz
M A
MA
Bevan
J A
JA
Fishman
M C
MC
D000594:Amino Acid Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D006706:Homeostasis; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D009154:Mutation; D019001:Nitric Oxide Synthase; D014664:Vasodilation / Q000502:physiology
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases