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, 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.
Kohlmann
O
O
Nephrology Division, Federal University of São Paulo, Brazil.
Cesaretti
M L
ML
Ginoza
M
M
Tavares
A
A
Zanella
M T
MT
Ribeiro
A B
AB
Ramos
O L
OL
Leeman
S E
SE
Gavras
I
I
Gavras
H
H
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*
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D014665:Vasodilator Agents; D013373:Substance P; D003900:Desoxycorticosterone; C066892:CP 96345