TY - JOUR
T1 - Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats
AU - Ruiz-Marcos, Francisco M.
AU - Clara Ortiíz, M.
AU - Fortepiani, Lourdes A.
AU - Nadal, Francisco J.A.
AU - Atucha, Noemií M.
AU - Garciía-Estañ, Joaquiín
N1 - Funding Information:
This work has been performed with grants from the Comisión Interministerial de Investigación Cientı́fica y Técnica of Spain (SAF97-0176) and Fundación Séneca de la Comunidad Autónoma de Murcia (PB/9/FS/99). M.C.O. (FP94-29000129), L.A.F. (PN95-42849602) and F.J.A.N. (AP98-22998855) are recipients of a predoctoral fellowship from the Ministerio de Educación y Cultura of Spain.
PY - 2001/2/2
Y1 - 2001/2/2
N2 - In the present study we analyzed mesenteric vascular reactivity of chronic nitric oxide (NO)-deficient hypertensive rats (NW-nitro-L-Arginine Methyl Ester, L-NAME, 50 mg/kg/day, oral, 3 weeks). Perfusion pressure changes in response to cumulative additions of methoxamine and KCl were significantly increased in the mesenteric vessels of the L-NAME-treated as compared with vessels of the controls. Verapamil reduced the responses to methoxamine, but those of the hypertensive rats were still enhanced. In contrast, responses to KCl were almost completely abolished by verapamil. In mesenteric vessels perfused with zero calcium and high-potassium Krebs, pressor responses to the re-addition of calcium were also significantly enhanced in the hypertensive rats compared to the controls. Vasodilator responses to acetylcholine in KCl-preconstricted vessels, while still significant, were reduced in the L-NAME-treated rats. In this case, acute inhibition of NO blocked the vasodilator responses to acetylcholine and abolished the differences between the two groups. In methoxamine-preconstricted vessels and in the presence of acute inhibition of NO and prostaglandins, vasodilator responses to acetylcholine were significantly greater in the hypertensive vessels than in controls. In conclusion, the mesenteric vessels of L-NAME hypertensive rats show an enhanced response to vasopressors which is related to calcium entry. These data also reveal the existence of an enhanced role of a NO and prostaglandin-independent vasodilator factor, probably endothelium-derived hyperpolarizing factor that may play a compensatory role in the deficiency of NO.
AB - In the present study we analyzed mesenteric vascular reactivity of chronic nitric oxide (NO)-deficient hypertensive rats (NW-nitro-L-Arginine Methyl Ester, L-NAME, 50 mg/kg/day, oral, 3 weeks). Perfusion pressure changes in response to cumulative additions of methoxamine and KCl were significantly increased in the mesenteric vessels of the L-NAME-treated as compared with vessels of the controls. Verapamil reduced the responses to methoxamine, but those of the hypertensive rats were still enhanced. In contrast, responses to KCl were almost completely abolished by verapamil. In mesenteric vessels perfused with zero calcium and high-potassium Krebs, pressor responses to the re-addition of calcium were also significantly enhanced in the hypertensive rats compared to the controls. Vasodilator responses to acetylcholine in KCl-preconstricted vessels, while still significant, were reduced in the L-NAME-treated rats. In this case, acute inhibition of NO blocked the vasodilator responses to acetylcholine and abolished the differences between the two groups. In methoxamine-preconstricted vessels and in the presence of acute inhibition of NO and prostaglandins, vasodilator responses to acetylcholine were significantly greater in the hypertensive vessels than in controls. In conclusion, the mesenteric vessels of L-NAME hypertensive rats show an enhanced response to vasopressors which is related to calcium entry. These data also reveal the existence of an enhanced role of a NO and prostaglandin-independent vasodilator factor, probably endothelium-derived hyperpolarizing factor that may play a compensatory role in the deficiency of NO.
KW - Acetylcholine
KW - Arterial hypertension
KW - EDHF (endothelium-dependent hyperpolarizing factor)
KW - Methoxamine
KW - Nitric oxide (NO)
KW - Vascular reactivity
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U2 - 10.1016/S0014-2999(00)00795-0
DO - 10.1016/S0014-2999(00)00795-0
M3 - Article
C2 - 11166291
AN - SCOPUS:0035793321
VL - 412
SP - 273
EP - 279
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -