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(Hypertension. 1997;29:506.)
© 1997 American Heart Association, Inc.

State-of-the-Art-Lecture

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

Osvaldo Kohlmann, Jr; Mario Luis Cesaretti; Milton Ginoza; Agostinho Tavares; Maria Teresa Zanella; Artur Beltrame Ribeiro; Oswaldo Luiz Ramos; Susan E. Leeman; Irene Gavras; Haralambos Gavras

From the Nephrology Division, Federal University of São Paulo, Brazil, and Department of Medicine, Boston (Mass) University Medical Center.

Correspondence to Osvaldo Kohlmann, Jr, Nephrology Division, Federal University of São Paulo, Rua Botucatu, 740, 04023-900, São Paulo, SP, Brazil

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.

Key Words: experimental hypertension • sodium-dependent hypertension • substance P • receptors NK-1 • tachykinins

Abbreviations: 1K-1C = one-kidney, one clip • 2K-1C = two-kidney, one clip • BP = blood pressure • HR = heart rate • MAP = mean arterial pressure • SHR = spontaneously hypertensive rats • WKY = Wistar-Kyoto rats

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