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 μg h−1 s.c, for 6 weeks), nor vehicle altered systolic blood...

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Published in:British journal of pharmacology 1993-03, Vol.108 (3), p.651-657
Main Authors: Madeddu, Paolo, Anania, Vittorio, Parpaglia, Paolo Pinna, Demontis, Maria Piera, Varoni, Maria Vittoria, Fattaccio, Maria Caterina, Glorioso, Nicola
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
blood pressure
Blood Pressure - drug effects
bradykinin
Bradykinin - analogs & derivatives
Bradykinin - antagonists & inhibitors
Bradykinin - pharmacology
Creatinine - blood
Creatinine - metabolism
Creatinine - urine
Desoxycorticosterone
Dinoprostone - blood
Drug toxicity and drugs side effects treatment
Heart Rate - drug effects
Hormones - blood
Hypertension - chemically induced
Hypertension - physiopathology
kallikrein
Kallikreins - urine
Kidney - drug effects
Kidney Function Tests
Kinin antagonist
Male
Medical sciences
mineralocorticoids
Pharmacology. Drug treatments
prostaglandins
Rats
Rats, Wistar
Receptors, Bradykinin
Receptors, Neurotransmitter - antagonists & inhibitors
renal function
Toxicity: cardiovascular system
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Summary: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 μg 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.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1993.tb12856.x