Cardiovascular effects of brain kinin receptor blockade in spontaneously hypertensive rats.
We studied the role of brain kinins in the regulation of cardiovascular function. Intracerebroventricular injection of 380 pmol bradykinin increased mean blood pressure by 20 +/- 2 mm Hg (P < .01) in normotensive Wistar-Kyoto (WKY) rats. Complete inhibition of this effect was achieved with intracerebroventricular administration of the newly synthesized, long-acting B2 receptor antagonist D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140). On a molar basis, Hoe 140 was two orders of magnitude more potent than antagonists of the first generation. Baroreceptor sensitivity, estimated as the heart rate response to blood pressure changes induced by intravenous injection of phenylephrine or sodium nitroprusside, was not altered by Hoe 140 in WKY rats. In spontaneously hypertensive rats (SHR), baroreceptor reflex sensitivity to increments in mean blood pressure was reduced by Hoe 140 (mean slope value: -0.47 +/- 0.07 versus -0.92 +/- 0.13 beats per minute per millimeter of mercury in controls, P < .05). Hoe 140 did not affect the tachycardic component of the baroreceptor reflex. Two-week intracerebroventricular infusion of Hoe 140 did not alter systolic blood pressure or heart rate in WKY rats. In SHR, systolic blood pressure increased (P < .01) similarly during the infusion of Hoe 140 or vehicle (from 174 +/- 6 to 220 +/- 5 mm Hg and 178 +/- 4 to 210 +/- 4 mm Hg at 2 weeks, respectively), whereas heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Madeddu
P
P
Clinica Medica and Farmacologia, University of Sassari, Italy.
Glorioso
N
N
Varoni
M V
MV
Demontis
M P
MP
Fattaccio
M C
MC
Anania
V
V
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D013045:Species Specificity
D065168:Bradykinin Receptor Antagonists; D009599:Nitroprusside; D010656:Phenylephrine; C065679:icatibant; D001920:Bradykinin