Blunted acetylcholine relaxation and nitric oxide release in arteries from renal hypertensive rats.
OBJECTIVE
Investigation of the effect of hypertension on endothelium-dependent relaxation and release of nitric oxide (NO) in normotensive and renal hypertensive rats.


METHODS
Sprague-Dawley rats were randomly allocated into two groups: uninephrectomized controls and one-kidney one-clip (Goldblatt hypertension) hypertensive rats, a non-renin dependent model of hypertension. After 10 weeks and in the presence of the cyclooxygenase inhibitor indomethacin, simultaneous measurements of the NO concentration, measured with a NO-specific microelectrode and endothelium-dependent relaxation were performed in isolated rat superior mesenteric arteries.


RESULTS
Addition of the NO scavenger, oxyhaemoglobin, showed that basal NO concentration was unaltered in arterial segments from hypertensive rats. In norepinephrine-contracted arteries, acetylcholine increased the NO concentration and caused relaxations, and both parameters were significantly reduced in renal hypertensive arteries. Relaxations induced by the NO donor, S-nitroso-N-acetylpenicillamine were reduced. The superoxide scavenger, superoxide dismutase, and the NO synthase substrate, l-arginine, did not change the increase in NO concentration or acetylcholine relaxation in arteries from normotensive or renal hypertensive animals. In contrast, the NO synthase inhibitor, asymmetric dimethyl l-arginine, reduced the NO concentration and acetylcholine relaxation, while these responses were abolished in the presence of oxyhaemoglobin.


CONCLUSIONS
This study provides direct evidence that reduced endothelium-dependent relaxations in the superior mesenteric artery from renal hypertensive rats is due, at least in part, to diminished NO release. The reduced NO release and relaxation persist in the presence of excess of substrate for NO synthase.
Stankevicius
Edgaras
E
Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark.
Martinez
Ana Cristina
AC
Mulvany
Michael J
MJ
Simonsen
Ulf
U
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D011092:Polyethylene Glycols; C018524:N,N-dimethylarginine; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D000109:Acetylcholine