TY - JOUR
T1 - Angiotensin II type 1 receptor blockade restores nitric oxide-dependent renal vascular responses in renovascular hypertension
AU - Martinez, Yolanda
AU - Martinez, Sonia
AU - Meaney, Alejandra
AU - Meaney, Eduardo
AU - Escalante, Bruno
PY - 2002/9
Y1 - 2002/9
N2 - 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 11 (1 μg) 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.
AB - 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 11 (1 μg) 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.
KW - Angiotensin II
KW - Hypertension
KW - Losartan
KW - Nitric oxide
KW - Nitrites
UR - http://www.scopus.com/inward/record.url?scp=0036708259&partnerID=8YFLogxK
U2 - 10.1097/00005344-200209000-00007
DO - 10.1097/00005344-200209000-00007
M3 - Artículo
SN - 0160-2446
VL - 40
SP - 381
EP - 387
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 3
ER -