Chronic kinin receptor blockade induces hypertension in deoxycorticosterone-treated rats.
1. The contribution of endogenous kinins to the regulation of blood pressure and renal function of Wistar rats was evaluated by use of the new B2-receptor antagonist, Hoe 140, (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). 2. Neither Hoe 140 (4 micrograms h-1 s.c., for 6 weeks), nor vehicle altered systolic blood pressure (SBP, tail-cuff plethysmography) or renal function in rats, under normal conditions. 3. Chronic administration of deoxycorticosterone (DOC, 25 mg kg-1 s.c., weekly) increased SBP slightly only after 6 weeks (from 124 +/- 2 to 133 +/- 3 mmHg, P < 0.05). An earlier and greater rise in SBP (P < 0.01) occurred when DOC was combined with chronic infusion of Hoe 140 (from 125 +/- 1 to 154 +/- 3, P < 0.01). The hypertensive effect of Hoe 140 was confirmed by direct measurement of mean blood pressure (143 +/- 2 vs 122 +/- 2 mmHg in controls, P < 0.01). 4. DOC caused an initial fall, followed by a transitory increase in urinary volume and sodium excretion; thereafter, both parameters returned to baseline. The initial antidiuretic and antinatriuretic effects were enhanced by Hoe 140 (P < 0.05). 5. Urinary prostaglandin E2 excretion was increased by DOC (from 106 +/- 3 to 153 +/- 4 ng 24 h-1, P < 0.01) and this effect was prevented by Hoe 140 (from 95 +/- 3 to 104 +/- 3 ng 24 h-1, NS). By contrast, the high urinary vasopressin excretion and suppressed plasma renin activity found in DOC-treated rats were not altered by Hoe 140. 6. These data suggest that endogenous kinins play an important role in the regulation of arterial blood pressure under conditions of mineralocorticoid excess.
Madeddu
P
P
Sassari University, Italy.
Anania
V
V
Parpaglia
P P
PP
Demontis
M P
MP
Varoni
M V
MV
Fattaccio
M C
MC
Glorioso
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003404:Creatinine / Q000097:blood / Q000378:metabolism / Q000652:urine; D003900:Desoxycorticosterone; D015232:Dinoprostone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*
D006728:Hormones; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D003900:Desoxycorticosterone; C065679:icatibant; D003404:Creatinine; D007610:Kallikreins; D015232:Dinoprostone; D001920:Bradykinin