Role of Substance P in Blood Pressure Regulation in Salt-Dependent Experimental Hypertension

The participation of substance P in the pathogenesis of five models of experimental hypertension, ie, DOCA-salt, subtotal nephrectomy, one-kidney-one clip renovascular, two-kidney-one clip renovascular, and spontaneous hypertension, was evaluated via an acute infusion of a newly synthesized potent,...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1997-01, Vol.29 (1), p.506-509
Main Authors: Kohlmann, Osvaldo Jr, Cesaretti, Mario Luis, Ginoza, Milton, Tavares, Agostinho, Zanella, Maria Teresa, Ribeiro, Artur Beltrame, Ramos, Oswaldo Luiz, Leeman, Susan E, Gavras, Irene, Gavras, Haralambos
Format: Article
Language:English
Subjects:
Animals
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Biphenyl Compounds - pharmacology
Blood and lymphatic vessels
Blood Pressure - drug effects
Blood Pressure - physiology
Cardiology. Vascular system
Desoxycorticosterone
Experimental diseases
Hypertension - chemically induced
Hypertension - physiopathology
Male
Medical sciences
Neurokinin-1 Receptor Antagonists
Rats
Rats, Inbred WKY
Substance P - antagonists & inhibitors
Substance P - physiology
Vasodilator Agents - pharmacology
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Summary:The participation of substance P in the pathogenesis of five models of experimental hypertension, ie, DOCA-salt, subtotal nephrectomy, one-kidney-one clip renovascular, two-kidney-one clip renovascular, and spontaneous hypertension, was evaluated via an acute infusion of a newly synthesized potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt, subtotal nephrectomy, and one-kidney-one clip renovascular hypertensive rats but only small and nonsignificant changes in blood pressure of two-kidney-one clip renovascular and spontaneously hypertensive rats. CP 96,345 had no effect on the blood pressure of sham-treated controls and Wistar-Kyoto rats. This NK-1 receptor antagonist did not significantly affect the heart rate of any experimental model studied. The data suggest that endogenous substance P may act as a partial counterregulatory mechanism against vasoconstriction in models of salt-dependent hypertension. (Hypertension. 1997;29[part 2]:506-509.)
ISSN:0194-911X
1524-4563
DOI:10.1161/01.hyp.29.1.506