Effects of Hoe 140, a bradykinin B2-receptor antagonist, on renal function in conscious normotensive rats.
1. The present study was designed to determine if endogenous kinins are involved in the regulation of arterial blood pressure and renal function in conscious rats given deoxycorticosterone enantate (DOC, 25 mg kg-1, s.c., weekly) or vehicle for two weeks. 2. The bradykinin B2-receptor antagonist, D-Arg[Hyp3,Thi5,D-Tic7,Oic8]- bradykinin (Hoe 140), at a dose of 300 micrograms kg-1, s.c., blocked the hypotensive effect of 300 ng kg-1 bradykinin i.a., but it did not alter the blood pressure lowering action of 300 ng kg-1 acetylcholine or prostaglandin E2. Inhibition of the response to bradykinin persisted up to 6 h after the administration of Hoe 140. 3. Administration of 300 micrograms kg-1 Hoe 140 s.c. four times a day did not alter mean blood pressure, renal blood flow, or renal function in rats given DOC-vehicle. However, it decreased urinary volume by 70% (from 48.2 +/- 3.8 to 14.3 +/- 3.7 ml 24 h-1, P less than 0.01) and urinary secretion of sodium by 54% (from 1.02 +/- 0.05 to 0.47 +/- 0.16 mmol 24 h-1, P less than 0.01) and potassium by 30% (from 2.93 +/- 0.15 to 2.04 +/- 0.15 mmol 24 h-1, P less than 0.05) in DOC-treated rats. Mean blood pressure, glomerular filtration rate and total renal blood flow remained unchanged. 4. Our results suggest that endogenous kinins play a role in the regulation of renal excretion of water and sodium in the presence of elevated levels of DOC.
Madeddu
P
P
Clinica Medica, Sassari University, Italy.
Anania
V
V
Parpaglia
P P
PP
Demontis
M P
MP
Varoni
M V
MV
Pisanu
G
G
Troffa
C
C
Tonolo
G
G
Glorioso
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000031:analogs & derivatives; D003900:Desoxycorticosterone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*
D016232:Endothelins; D009842:Oligopeptides; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D000804:Angiotensin II; D010656:Phenylephrine; D003900:Desoxycorticosterone; C065679:icatibant; D015232:Dinoprostone; D000109:Acetylcholine; D001920:Bradykinin