Effects of Hoe 140, a bradykinin B₂‐receptor antagonist, on renal function in conscious normotensive rats

Abstract

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-', 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 gg kg-', s.c., blocked the hypotensive effect of 300 ng kg-' bradykinin i.a., but it did not alter the blood pressure lowering action of 300 ng kg-' 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 fg kg-' 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-', P<0.01) and urinary secretion of sodium by 54% (from 1.02 ± 0.05 to 0.47 ± 0.16 mmol 24 h-', P<0.01) and potassium by 30% (from 2.93 ± 0.15 to 2.04 ± 0.15 mmol 24 h-', P<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.

Contribution of Bradykinin B2 Receptors to the Inhibition by Valsartan of Systemic and Renal Effects of Exogenous Angiotensin II in Salt-Repleted Humans

“…In contrast, HOE140 accentuated the elevation in MBP and the fall in UNaV, indicating that endogenous BK opposes in humans the effects of infused AngII on BP and UNaV. This agrees with the potentiated hypertension and sodium retention with BKB2R blockade in desoxycorticosterone acetate-salt or AngII-infused rats (Madeddu et al, 1992(Madeddu et al, , 2007 and human data showing a slightly increased baseline BP with high-dose HOE140 (Squire et al, 2000) and a higher BP with BKB2R blockade after RAS stimulation with furosemide .…”

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B 2 Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

“…Hence, it is now well established that BK causes vasodilation and natriuresis and exerts anti-ischemic, antiproliferative, and antiatherosclerotic effects through the activation of the B 2 receptor. 18,19 Endogenous BK contributes to the favorable effects of ACE inhibitors on blood pressure, on ischemic preconditioning, and on myocardial remodeling after infarction. 20 The present study extends these observations on the role of BK in vascular physiology.…”

Type 2 Bradykinin-Receptor Antagonism Does Not Modify Kinin or Angiotensin Peptide Levels

“…T he nonapeptide bradykinin [BK (1)(2)(3)(4)(5)(6)(7)(8)(9)] has important actions on blood vessels, heart, and kidney. There are 2 types of kinin receptor, the type 1 (B 1 ) and the type 2 (B 2 ) receptors.…”

“…There are 2 types of kinin receptor, the type 1 (B 1 ) and the type 2 (B 2 ) receptors. By far the most important hemodynamic effect of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) in vivo is the hypotensive vasodilatation produced by stimulation of endothelial B 2 receptors of arteries and arterioles, with subsequent endothelial release of nitric oxide and prostaglandins. 1 Additional renal actions of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) include the production of diuresis and natriuresis.…”

“…By far the most important hemodynamic effect of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) in vivo is the hypotensive vasodilatation produced by stimulation of endothelial B 2 receptors of arteries and arterioles, with subsequent endothelial release of nitric oxide and prostaglandins. 1 Additional renal actions of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) include the production of diuresis and natriuresis. 2,3 Whereas the diuretic effect of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) administered by the renal artery is mediated by B 2 receptors, both B 1 and B 2 receptors may participate in BK(1-9)-induced natriuresis and increase in renal blood flow.…”