Kinin actions on renal papillary blood flow and sodium excretion.

Abstract

Infusion of bradykinin into the renal medullary interstitium (0.1 /ig/min, n=6) significantly increased renal papillary blood flow as measured by laser-Doppler flowmetry to 117±3% of control without altering cortical blood flow or blood pressure in anesthetized Munich-Wistar rats. In animals prepared for clearance studies, renal medullary bradykinin infusion did not alter total renal blood flow, glomerular filtration rate, or renal interstitial hydrostatic pressure but increased urine flow by 100%, sodium excretion by 111%, and fractional sodium excretion by 107%. No changes occurred in mean arterial pressure or contralateral kidney function during the interstitial bradykinin infusion. Blockade of endogenous kinin degradation by interstitial infusion of captopril (1 mg/hr) significantly increased papillary blood flow by 21 ±5% without altering cortical blood flow. Pretreatment with the nitric oxide inhibitor jV c -nltro-L-arginine-methyI ester (2 fig/mia, n=l) eliminated the increase in papillary blood flow associated with either bradykinin or captopril infusion. We conclude that renal medullary interstitial infusion of bradykinin increases sodium and water excretion, which is associated with a selective increase in papillary blood flow by a nitric oxide-dependent mechanism. kinins may act as paracrine agents in the renal medulla. 1 " 3 Intravenous administration of an inhibitor of neutral endopeptidase, the major kininase in the rat kidney, 4 selectively increased renal inner medullary (papillary) blood flow in anesthetized rats.3 This effect was blocked by a kinin receptor antagonist, indicating that an elevation of endogenous kinins can alter medullary blood flow. Similar results have been demonstrated during angiotensin converting enzyme inhibition. Although cortical blood flow increases during inhibition of converting enzyme because of decreased angiotensin II levels, renal medullary blood flow increases because of increased kinins. 6 ' 7 These data indicate that kinins have a primary influence on the renal medullary circulation in the rat. In support of these functional data, morphological data indicate that the intrarenal site of kinin formation and release is in the distal connecting tubule and collecting duct. 1 -3 It is therefore thought that the peptide exerts its physiological effects from the luminal or the interstitial side of the collecting duct in the renal medulla. Previous studies examining the renal hemodynamic and excretory effects of exogenous bradykinin were performed by renal arterial infusion. "10 This route of infusion may not mimic a physiological route of kinin delivery, because intrarenally formed kinins must reach the vasculature via the interstitium. To address this problem, we have recently developed an infusion technique in our laboratory by which compounds can be infused and localized in the renal medullary interstitium. 1112The purpose of the present study was to characterize the effects of renal medullary interstitial infusion of bradykinin on the intrarenal distribution o...

Cardiovascular Phenotypes of Kinin B 2 Receptor– and Tissue Kallikrein–Deficient Mice

“…Regarding the coronaries, our dynamic experiments show that local resistance is de- Ϫ/Ϫ mice. A potential role for bradykinin in the regulation of coronary resistance and/or blood flow has previously been hypothesized, [31][32][33][34] but to our knowledge, the present study is the first to document in vivo the consequences of a constitutive deficiency of the B 2 receptor in this vascular bed. As expected, dipyridamole infusion elicits no renal vasodilatation in B 2 Ϫ/Ϫ and WT mice, thus confirming the selectivity of this vasodilator agent for the coronary vasculature.…”

Role of renal NO production in the regulation of medullary blood flow

“…No changes of cortical flow were observed. Similarly, infusions of bradykinin (57) and acetylcholine (62), NO-dependent vasodilators, also produced substantial increases of MBF. Several important conclusions were drawn from these in vivo studies in anesthetized rats.…”

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

“…Changes in renal CBF are not always replicated in the medullary or papillary regions because medullary hemodynamics can be regulated independently of renal CBF (Pallone et al 1990, Navar et al 1996, Mattson 2003. Vasoactive agents, including AngII, dopamine, arginine vasopressin, atrial natriuretic peptide, and bradykinin have been demonstrated to induce renal region-specific hemodynamic changes (Takezawa et al 1987, Pallone et al 1990, Nobes et al 1991, Mattson & Cowley 1993, Heyman et al 1995, Badzynska et al 2002, Igbe et al 2012. However, the effect of UII on regional RBF was unclear.…”