title: Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats.
abstract: The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.
authors.affiliation: Department of Patologia Medica, University of Sassari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Madeddu
authors.forename: N
authors.initials: N
authors.lastname: Glorioso
authors.forename: A
authors.initials: A
authors.lastname: Soro
authors.forename: G
authors.initials: G
authors.lastname: Tonolo
authors.forename: P
authors.initials: P
authors.lastname: Manunta
authors.forename: C
authors.initials: C
authors.lastname: Troffa
authors.forename: M P
authors.initials: MP
authors.lastname: Demontis
authors.forename: M V
authors.initials: MV
authors.lastname: Varoni
authors.forename: V
authors.initials: V
authors.lastname: Anania
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007705:Kinins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012016:Reference Values
chemical_list: D007705:Kinins; D002216:Captopril