Angiotensin II type 1 receptor blockade restores nitric oxide-dependent renal vascular responses in renovascular hypertension.
It was previously reported that enhancement of renal vascular responses to angiotensin II in hypertensive rats is related to decreased release of nitric oxide. Thus, it was suggested that impairment of nitric oxide synthesis during development of hypertension is related to a decreased nitric oxide synthase mRNA expression by an angiotensin II-dependent mechanism. The current study evaluated whether the blockade of angiotensin II type 1 receptor during the development of hypertension restored nitric oxide synthase mRNA expression, nitric oxide synthesis, and nitric oxide-dependent modulation of angiotensin II vasoconstrictor effects. It was shown that losartan treatment prevented increased vascular responses to angiotensin II in hypertensive rats and that this effect was associated with restoration of nitric oxide synthase mRNA expression and nitric oxide synthase activity. Furthermore, angiotensin II-dependent nitric oxide release in hypertensive rats was potentiated by losartan treatment. Angiotensin II (1 microg) released renal nitrites by 485 +/- 178, 470 +/- 150, 185 +/- 45, and 515 +/- 100 nmol/ml/30 s in the kidneys from normotensive, losartan-treated normotensive rats, hypertensive, and losartan-treated hypertensive rats, respectively. The data suggest that during development of hypertension, angiotensin II downregulates nitric oxide synthase mRNA expression, blunting nitric oxide vasodilatory tone and increasing vascular sensitivity to vasoconstrictor agents in the renal circulation.
Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN, México City, Mexico.
Yolanda
Y
Martinez
Sonia
S
Martinez
Alejandra
A
Meaney
Eduardo
E
Meaney
Bruno
B
Escalante
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006977:Hypertension, Renal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase