Chronic inhibition of bradykinin receptors alters cardiovascular function in rats with an excess of circulating vasoconstrictors.
1. The contribution of endogenous kinins to the regulation of blood pressure of angiotensin-treated rats was evaluated using the new bradykinin B2-receptor antagonist Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). 2. Chronic intraperitoneal infusion of 20 nmol/day angiotensin II did not alter systolic blood pressure or plasma angiotensin II levels. A significant increase in plasma aldosterone and corticosterone levels was observed after 4 weeks (from 89 +/- 20 to 140 +/- 22 and from 147 +/- 30 to 225 +/- 33 pg/ml, respectively; P < 0.05). 3. Combined administration of 20 nmol/day angiotensin II and 75 nmol Hoe 140 induced a significant increase in systolic blood pressure from 126 +/- 3 to 142 +/- 3 and 137 +/- 3 mmHg, at 1 and 4 weeks, respectively (P < 0.05). This effect was not accompanied by significant changes in plasma angiotensin II concentration. The angiotensin-induced increase in plasma levels of aldosterone and corticosterone was not altered by the antagonist Hoe 140. 4. These findings indicate that blockade of endogenous kinin receptors enhances the slow pressor effect induced by angiotensin II. Therefore, endogenous kinins may play a role in preventing the cardiovascular effects of an excess of vasoconstrictors.
Madeddu
P
P
Clinica Medica e Farmacologia, Università di Sassari, Italy.
Pinna-Parpaglia
P
P
Varoni
M V
MV
Demontis
M P
MP
Fattaccio
M C
MC
Anania
V
V
Glorioso
N
N
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002320:Cardiovascular Physiological Phenomena; D003345:Corticosterone / Q000097:blood; D007705:Kinins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D000804:Angiotensin II; D000450:Aldosterone; C065679:icatibant; D001920:Bradykinin; D003345:Corticosterone