EDRF‐mediated dilatation in the rat isolated perfused kidney: a microangiographic study

Burton, G. A.; Griffith, T. M.; Edwards, David Hughes

doi:10.1111/j.1476-5381.1989.tb12666.x

Cited by 13 publications

(5 citation statements)

References 20 publications

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“…This finding agrees with previous observations from our laboratory [3], and with the inability of hemoglobin (a blocker of NO action) to change RPP in the rat isolated perfused kidney [21] . In this connection, Adeagbo et al [20] recently reported that L-NAME ( 10~4 M ) had no effect on the bas al tone in the mesenteric vascular bed.…”

Section: Discussionsupporting

confidence: 93%

Modulatory Role of Endothelium-Derived Relaxing Factors on the Response to Vasoconstrictors and Flow-Pressure Curve in the Isolated Perfused Rat Kidney

Vargas

Osuna²

1996

J Vasc Res

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The aim of this study was to compare the effects of the blockade of nitric oxide (NO) and of endothelium-derived hyperpolarizing factor (EDHF) on the response to vasoconstrictors (VC) and on the flow-pressure curve in the isolated perfused rat kidney. To this end, dose-response curves to phenylephrine and BaCl₂ were studied in the renal vasculature under basal conditions and after the infusion of N^ω-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA) in endothelium-intact and endothelium-denuded (CHAPS-treated) preparations. In another experiment, renal flow-pressure curves were obtained under basal conditions and after the infusion of L-NAME or TEA. The flow-pressure curve was obtained by increasing renal perfusion flow (RPF) from 2.5 to 15 ml/min/g kidney weight (KW) over the basal level (5 ml/min/g KW). L-NAME or TEA produced a leftward shift of the dose-response curves of both VC, and the simultaneous administration of L-NAME and TEA produced a greater shift to the left in the pressor response curves. CHAPS treatment produced a leftward shift of the dose-response curves of both VC, and the dose-response curves were not significantly modified by the infusion of L-NAME or TEA. L-NAME markedly shifted the flow-pressure curve upward, especially at higher levels of RPF. However, the administration of TEA, perfusate solution (Tyrode) or L-NAME did not significantly change the flow-pressure curve. These results suggest that NO is released in response to VC as well as to increased perfusion flow in the isolated renal vascular bed. However, EDHF release seems to be stimulated by VC but not by increased perfusion flow.

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Section: Discussionsupporting

confidence: 93%

Modulatory Role of Endothelium-Derived Relaxing Factors on the Response to Vasoconstrictors and Flow-Pressure Curve in the Isolated Perfused Rat Kidney

Vargas

Osuna²

1996

J Vasc Res

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“…It is of interest that the dilatation was observed in the presence of NAME and thus occurs independently of EDRF activity. This phenomenon has also been shown to occur in this preparation in response to other constrictor stimuli such as haemoglobin (Griffith et al, 1987; i 0 9 M 0 1989), in the rat kidney in response to the a1-adrenoceptor agonist methoxamine (Burton et al, 1989) and magnetic resonance imaging has shown that, in vivo, phenylephrine causes passive distension of the rat carotid artery (Behling et al, 1989). The lack of activity of endothelin-l in the central artery is unusual as endothelin-l is known to constrict a variety of large conduit vessels (Yanagisawa et al, 1988;D'Orleans-Juste et al, 1988).…”

Section: Discussionmentioning

confidence: 84%

Activities of endothelin‐1 in the vascular network of the rabbit ear: a microangiographic study

Randall¹,

Edwards

Griffith³

1990

British J Pharmacology

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1 The effects of endothelin-1 on perfusion pressure and on arterial and venous diameters were examined simultaneously in a rabbit isolated ear preparation perfused with physiological buffer. The effects of hypoxia and inhibition of endothelium-derived relaxant factor (EDRF) activity on vascular responses to endothelin-1 were also investigated.2 Endothelin-1 was potent at increasing perfusion pressure (ED50 = 46.7 + 11.0 pmol; R.,, = 85.3 + 5.3 mmHg). The potency and maximum reactivity were not significantly affected by hypoxia, inhibition of EDRF activity with 50,UM N-nitro-L-arginine methyl ester (NAME) or a combination of hypoxia and NAME. 3 Endothelin-1 caused equipotent dose-dependent constrictions of the first four generations of arterial branch vessels (G1-G4) but did not influence the diameter of the central ear artery except at high doses of the peptide when 'paradoxical dilatation' was observed. The peptide was also equipotent at causing constriction of the smaller venous vessels (V1-V4) but did not affect the large veins (VO). 4 Under conditions of hypoxia the potency of endothelin-1 was reduced in G2 and G3, was unaffected in G4 and the peptide did not significantly constrict either Go or G1. Hypoxia reduced the potency of endothelin-1 in the smaller venous vessels (V1-V4), but conversely unmasked a marked constriction of the large veins (VO), which was not observed under normoxic conditions. 5 NAME 5OpUM abolished the vasodilator effects of acetylcholine in this preparation. Inhibition of EDRF activity with NAME under normoxic conditions did not influence the constrictor activity of endothelin-1 on the arterial or venous branch vessels. However, inhibition of EDRF activity under hypoxic conditions prevented the reduction of potency of endothelin-1 as a constrictor of arterial and venous branch vessels which occurred in hypoxia. In the presence of NAME endothelin-1 constricted VO in both normoxia and hypoxia with equipotency but the maximum effect was greatest in hypoxia. 6 In conclusion, endothelin-1 is a powerful vasoconstrictor which acts with greater potency in veins than arteries in the rabbit isolated ear. Although hypoxia does not influence pressor responses it nevertheless alters the spatial pattern of vasoconstriction. In particular hypoxia unmasks constriction of the large veins by endothelin-1. Constriction of these veins was also observed in the absence of EDRF in normoxia, but to a much lesser degree so that the effect of hypoxia may only be partially due to reduced EDRF activity. Hypoxia may therefore directly or indirectly increase the sensitivity of the main veins to endothelin-1.

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“…With one exception [24], in most studies on the role of NO in the regulation of renal function, which were performed in rats and dogs [for review see, [1][2][3] and also in isolated rat kidney preparations [25][26][27], NOS inhibition by L-ARG analogs has led to renal vasoconstriction. These findings -as opposed to the vasodilation induced by L-ARG [28] support the concept that the renal vasculature is under a 'tonic' influence of NO.…”

Section: Discussionmentioning

confidence: 99%

Relative Roles of Nitric Oxide, Prostanoids and Angiotensin II in the Regulation of Canine Glomerular Hemodynamics

Kramer

Horáček

Bäcker

et al. 2004

Kidney Blood Press Res

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Glomerular hemodynamics are controlled by a variety of physical, nervous and hormonal factors including the potent vasoconstrictors, angiotensin (ANG) II and endothelin-1 (ET-1), and the vasodilator prostanoids (prostaglandin = PG) and nitric oxide (NO). Since no micropuncture data on the canine kidney exist with respect to the relative roles of the endogenous vasoactive hormones/autacoids NO, PG and ANG II in modulating glomerular hemodynamics, in the present study using the micropuncture technique in anesthetized dogs on a normal salt intake, we investigated the relative effects of these hormones/autacoids by means of the L-arginine analog, N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME), a competitive NO synthase (NOS) inhibitor, the cyclooxygenase inhibitor indomethacin (INDO), and the AT₁ receptor blocker EXP 3174. An intrarenal arterial (i.r.a.) bolus (within 5 min) of 2.5 mg of L-NAME led to a significant decrease in total renal blood flow (RBF) and single nephron glomerular blood flow (SNGBF) from 4.46 ± 0.51 to 3.52 ± 0.41 ml/min/g kidney weight and from 0.393 ± 0.041 to 0.341 ± 0.037 µl/min (p < 0.01), respectively, without a change in glomerular filtration rate (GFR). The increase in arteriolar resistance was more pronounced at the efferent (+31%) than at the afferent (+13%) arteriole, and K_f decreased from 4.5 ± 0.5 to 3.7 ± 0.4 nl/min/mm Hg (p < 0.01). INDO (5 mg/kg i.v. bolus followed by 0.17 mg/kg/min i.v.) had no effect on glomerular hemodynamics. EXP 3174 (30 µg/kg/min i.r.a.) increased RBF and SNGBF from 4.35 ± 0.45 to 4.99 ± 0.50 ml/min/g kidney weight and from 0.403 ± 0.028 to 0.478 ± 0.039 µl/min (p < 0.01), respectively, without an effect on GFR. It reduced the efferent arteriolar resistance by 25% as compared to 13% at the afferent arteriolar level. EXP 3174 increased K_f from 5.1 ± 0.4 to 8.1 ± 0.6 mm Hg (p < 0.01) in the presence of a decrease in effective filtration pressure from 13.2 ± 1.7 to 8.3 ± 1.0 mm Hg (p < 0.01). The glomerular hemodynamic effects of L-NAME were unaltered by pretreatment with INDO or EXP 3174, whereas its tubular effects were restored in the presence of EXP 3174. Thus, from these first micropuncture data in the anesthetized dog on a normal sodium intake we conclude that (1) acute intrarenal inhibition of NOS by L-NAME decreases RBF and SNGBF due to vasoconstriction of the afferent and, more pronounced, efferent arterioles. Since L-NAME simultaneously decreases K_f, GFR remains unaltered. (2) These renal hemodynamic effects of NOS inhibition were not mediated by prostanoids or intrarenal ANG II. Thus, the tonic activity of intrarenal NOS plays an important role in maintaining glomerular hemodynamics in the canine kidney.

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EDRF‐mediated dilatation in the rat isolated perfused kidney: a microangiographic study

Cited by 13 publications

References 20 publications

Modulatory Role of Endothelium-Derived Relaxing Factors on the Response to Vasoconstrictors and Flow-Pressure Curve in the Isolated Perfused Rat Kidney

Modulatory Role of Endothelium-Derived Relaxing Factors on the Response to Vasoconstrictors and Flow-Pressure Curve in the Isolated Perfused Rat Kidney

Activities of endothelin‐1 in the vascular network of the rabbit ear: a microangiographic study

Relative Roles of Nitric Oxide, Prostanoids and Angiotensin II in the Regulation of Canine Glomerular Hemodynamics

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