title: Role of substance P in blood pressure regulation in salt-dependent experimental hypertension.
abstract: 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.
authors.affiliation: Nephrology Division, Federal University of São Paulo, Brazil.
authors.forename: O
authors.initials: O
authors.lastname: Kohlmann
authors.forename: M L
authors.initials: ML
authors.lastname: Cesaretti
authors.forename: M
authors.initials: M
authors.lastname: Ginoza
authors.forename: A
authors.initials: A
authors.lastname: Tavares
authors.forename: M T
authors.initials: MT
authors.lastname: Zanella
authors.forename: A B
authors.initials: AB
authors.lastname: Ribeiro
authors.forename: O L
authors.initials: OL
authors.lastname: Ramos
authors.forename: S E
authors.initials: SE
authors.lastname: Leeman
authors.forename: I
authors.initials: I
authors.lastname: Gavras
authors.forename: H
authors.initials: H
authors.lastname: Gavras
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D011921:Rats, Inbred WKY; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D014665:Vasodilator Agents; D013373:Substance P; D003900:Desoxycorticosterone; C066892:CP 96345