Regulation of intrarenal blood flow in experimental  heart failure: role of endothelin and nitric oxide

Congestive heart failure (CHF) is associated with a marked decrease in cortical blood flow and preservation of medullary blood flow. In the present study we tested the hypothesis that changes in the endothelin (ET) and nitric oxide (NO) systems in the kidney may contribute to the altered intrarenal hemodynamics in rats with aortocaval fistula, an experimental model of CHF. Cortical and medullary blood flow were measured simultaneously by laser-Doppler flowmetry in controls and rats with compensated and decompensated CHF. As previously reported [K. Gurbanov, I. Rubinstein, A. Hoffman, Z. Abassi, O. S. Better, and J. Winaver. Am. J. Physiol. 271 ( Renal Fluid Electrolyte Physiol. 40): F1166–F1172, 1996], administration of ET-1 in control rats produced a sustained cortical vasoconstriction and a transient medullary vasodilatory response. In rats with decompensated CHF, cortical vasoconstriction was severely blunted, whereas ET-1-induced medullary vasodilation was significantly prolonged. This prolonged response was mimicked by IRL-1620, a specific ETB agonist, and partially abolished by NO synthase (NOS) blockade. In line with these findings, expression of ET-1, ETA and ETB receptors, and endothelial NOS (eNOS), assessed by RT-PCR, and eNOS immunoreactivity, assessed by Western blotting, was significantly higher in the medulla than in the cortex. Moreover, expression of ET-1 mRNA in the cortex and eNOS mRNA in the cortex and the medulla increased in proportion to the severity of heart failure. These findings indicate that CHF is associated with altered regulation of intrarenal blood flow, which reflects alterations in expression and activity of the ET and NO systems. It is further suggested that exaggerated NO activity in the medulla contributes to preservation of medullary blood flow in the face of cortical vasoconstriction in CHF.

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Role of renal medullary adenosine in the control of blood flow and sodium excretion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.3.r790 ◽

1999 ◽

Vol 276 (3) ◽

pp. R790-R798 ◽

Cited By ~ 40

Author(s):

Ai-Ping Zou ◽

Kasem Nithipatikom ◽

Pin-Lan Li ◽

Allen W. Cowley

Keyword(s):

Blood Flow ◽

Sodium Excretion ◽

Renal Medulla ◽

Urine Flow ◽

Doppler Flowmetry ◽

Blood Flows ◽

Medullary Blood Flow ◽

Adenosine Concentration ◽

Interstitial Infusion

This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 ± 5.2 nM, which was significantly higher than 55.6 ± 5.3 nM in the renal cortex ( n = 9). Renal medullary interstitial infusion of a selective A1antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol ⋅ kg−1 ⋅ min−1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX; 150 pmol ⋅ kg−1 ⋅ min−1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol ⋅ kg−1 ⋅ min−1( n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3receptor agonist, N 6-benzyl-5′-( N-ethylcarbonxamido)adenosine (300 pmol ⋅ kg−1 ⋅ min−1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.

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The Role of Neuronal Nitric Oxide Synthase in Regulation of Cerebral Blood Flow in Normocapnia and Hypercapnia in Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1995.97 ◽

1995 ◽

Vol 15 (5) ◽

pp. 774-778 ◽

Cited By ~ 128

Author(s):

Qiong Wang ◽

Dale A. Pelligrino ◽

Verna L. Baughman ◽

Heidi M. Koenig ◽

Ronald F. Albrecht

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Nitric Oxide Synthase ◽

Inhibitory Action ◽

Neuronal Nitric Oxide Synthase ◽

Muscarinic Agonist ◽

Doppler Flowmetry ◽

Nos Inhibitors ◽

Oxide Synthase

The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg−1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19–27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood–brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.

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Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

Brazilian Journal of Medical and Biological Research ◽

10.1590/s0100-879x2008000200014 ◽

2008 ◽

Vol 41 (2) ◽

pp. 170-175 ◽

Cited By ~ 4

Author(s):

S.I Gomez ◽

D.M. Strick ◽

J.C. Romero

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Medullary Blood Flow ◽

Renal Medullary Blood Flow

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Influence of the renal medullary circulation on the control of sodium excretion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.265.5.r963 ◽

1993 ◽

Vol 265 (5) ◽

pp. R963-R973 ◽

Cited By ~ 16

Author(s):

R. J. Roman ◽

A. P. Zou

Keyword(s):

Blood Flow ◽

Renal Perfusion ◽

Sodium Reabsorption ◽

Doppler Flowmetry ◽

Medullary Blood Flow ◽

Tubular Sodium Reabsorption ◽

Vasa Recta ◽

Urinary Concentrating Ability ◽

Reliable Methods

Although the role of the renal medullary circulation in the control of urinary concentrating ability is well established, its potential influence on tubular sodium reabsorption is not generally recognized. Nearly 30 years ago, changes in the intrarenal distribution of blood flow were first proposed to contribute to the natriuretic response to volume expansion. However, the lack of reliable methods for studying medullary blood flow limited progress in this area. The recent development of laser-Doppler flowmetry and videomicroscopic techniques for the study of the vasa recta circulation has renewed interest in the role of medullary hemodynamics in the control of sodium reabsorption. Results of these studies indicate that changes in renal medullary hemodynamics alter renal interstitial pressure and the medullary solute gradient and play an important role in the natriuretic response to elevations in renal perfusion pressure, intravenous infusion of saline, and changes in tubular sodium reabsorption produced by vasoactive compounds. What is emerging from these studies is the view that changes in renal medullary hemodynamics represent an important but misunderstood and long-ignored factor in the control of tubular sodium reabsorption.

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The intrarenal blood flow distribution and role of nitric oxide in diabetic rats

Metabolism ◽

10.1016/j.metabol.2005.01.023 ◽

2005 ◽

Vol 54 (6) ◽

pp. 788-792 ◽

Cited By ~ 3

Author(s):

Kazushige Nakanishi ◽

Shizuka Onuma ◽

Mariko Higa ◽

Yohko Nagai ◽

Toshiki Inokuchi

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Flow Distribution ◽

Diabetic Rats ◽

Blood Flow Distribution ◽

Intrarenal Blood Flow

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Role of nitric oxide in vasodilator response induced by salbutamol in rat diaphragmatic microcirculation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.5.h2173 ◽

1997 ◽

Vol 272 (5) ◽

pp. H2173-H2179 ◽

Cited By ~ 3

Author(s):

H. Y. Chang

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cyclic Amp ◽

Laser Doppler Flowmetry ◽

Ringer Solution ◽

Laser Doppler ◽

Microvascular Blood Flow ◽

Doppler Flowmetry ◽

Vasodilator Response

To determine the contribution of nitric oxide (NO) to the vasodilator response induced by salbutamol in diaphragmatic microcirculation, we studied a diaphragmatic preparation in anesthetized rats. With bicarbonate-buffered Ringer solution continuously suffusing the diaphragm, laser-Doppler flowmetry was used to record microvascular blood flow (QLDF). The drugs were applied to the surface of the diaphragm. Salbutamol (3.2 x 10(-7)-10(-4) M), isoproterenol (3.2 x 10(-8)-3.2 x 10(-6) M), and forskolin (3.2 x 10(-7)-10(-5) M) each elicited a concentration-dependent increase in QLDF. The vasodilator response induced by salbutamol (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was attenuated by a 15-min suffusion of N omega-nitro-L-arginine (L-NNA, 10(-4) M), and pretreatment with L-arginine (10(-2) M) could restore salbutamol-induced vasodilator responses. Salbutamol-induced vasodilation was also abolished by propranolol (10(-5) M). Similarly, the vasodilator response elicited by isoproterenol (3.2 x 10(-8), 10(-7), and 3.2 x 10(-7) M) and forskolin (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was inhibited by L-NNA (10(-4) M). In contrast, the vasodilator response induced by adenosine (10(-6), 10(-5), and 10(-4) M) was not affected by L-NNA (10(-4) M). These data indicate that in rat diaphragmatic microcirculation salbutamol-induced vasodilation may be partly mediated by beta-adrenoceptors on the endothelium. Moreover, these data suggest that an elevation of cyclic AMP in the endothelium may cause release of NO.

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Examination of the role of nitric oxide for the hypercapnic rise of cerebral blood flow in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.4.h1457 ◽

1994 ◽

Vol 266 (4) ◽

pp. H1457-H1464 ◽

Cited By ~ 4

Author(s):

M. Fabricius ◽

M. Lauritzen

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Topical Application ◽

Baseline Level ◽

Spreading Depression ◽

Doppler Flowmetry ◽

Perivascular Nerves ◽

Oxide Synthase

We examined the effect of nitric oxide synthase (NOS) inhibition and tetrodotoxin (TTX) on the increase of cerebral blood flow (CBF) in parietal (CoBF) and cerebellar cortex (CeBF) in response to hypercapnia. Rats were anesthetized with halothane and artificially ventilated. Hypercapnia was induced by adding 5% CO2 to the inhalation mixture. CoBF and CeBF were measured by laser-Doppler flowmetry. NOS inhibition was achieved by intravenous (30 mg/kg) and/or topical application (1 mM) of NG-nitro-L-arginine (L-NNA). Activity in perivascular nerves around pial and cortical vessels was inhibited by topical application of TTX (20 microM). Under control conditions, hypercapnia (66 +/- 1 mmHg) increased CoBF by 70 +/- 4% and CeBF by 96 +/- 5%. Systemic L-NNA decreased the baseline level of CoBF and CeBF by 11 +/- 3%, but topical L-NNA did not affect baseline flow. Intravenous L-NNA attenuated the hypercapnic increase of CoBF by 77 +/- 5% and CeBF by 63 +/- 4% within 10-20 min. Topical L-NNA attenuated the hypercapnic increase of CoBF by 52 +/- 6% and CeBF by 29 +/- 5% after 45-min exposure. Both CoBF and CeBF decreased rapidly when L-NNA was infused during sustained hypercapnia, but not when L-NNA was applied topically. Effect of intravenous L-NNA was partially prevented by pretreatment with intravenous L-arginine. Intravenous or topical L-NNA enhanced the rise of CBF elicited by cortical spreading depression, adenosine (1 mM), or sodium nitroprusside (300 microM), except in the cerebellum where topical L-NNA attenuated the rise of CBF elicited by adenosine by 53%.(ABSTRACT TRUNCATED AT 250 WORDS)

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Renal cortical and medullary blood flow responses during water restriction: role of vasopressin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.6.r1257 ◽

1996 ◽

Vol 270 (6) ◽

pp. R1257-R1264 ◽

Cited By ~ 18

Author(s):

K. G. Franchini ◽

A. W. Cowley

Keyword(s):

Blood Flow ◽

Urine Osmolality ◽

Control Group ◽

Water Restriction ◽

Vascular Effect ◽

Doppler Flowmetry ◽

Medullary Blood Flow ◽

Urinary Concentrating Ability ◽

Interstitial Infusion

Experiments were performed in unanesthetized rats to determine responses to 48 h water restriction of the renal regional microcirculation (cortex, outer medulla, and inner medulla) using implanted optical fibers and laser-Doppler flowmetry. The role of vasopressin (AVP) as a mediator of renal regional blood low changes and its contribution to urinary concentrating ability were assessed by continuous intramedullary interstitial infusion of specific V1 receptor antagonist d(CH2)5 [Tyr-(Me)2, Ala-NH2]AVP (2ng . kg-1 . min-1). Inner medullary blood flow decreased 34% at the end of 48 h of water restriction, whereas cortical and outer medullary flow did not change. This fall in inner medullary blood flow was substantially attenuated (18%) by the continuous interstitial infusion of the antagonist. Plasma AVP levels increased from control levels of 3.4 +/- 1.1 to 20.5 +/- 5.4 pg/ml (P < 0.05) by the end of the 48-h period of water restriction. Arterial pressure increased slightly but significantly during water restriction in the control rats. Infusion of antagonist impaired the maximal urinary concentrating ability, as demonstrated by the lower urine osmolality in this group than in the control group (1,893 +/- 49 vs. 2,419 +/- 225 mosmol/kg H2O; P < 0.05) measured during the second day of water restriction. Sodium and urea concentration decreased 20 and 22%, respectively, indicating that both contributed to the lower urine osmolality observed in the group of rats receiving the antagonist. We conclude that water restriction induces a selective decrease in inner medullary blood flow, which is mediated almost completely by endogenously released AVP. This vascular effect of AVP contributes to the maximum concentrating ability of the kidney.

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