Regional heterogeneity of endothelium‐dependent vasodilatation in the rabbit kidney.

Abstract

SUMMARY1. Regional heterogeneity of endothelial function exists but its role in the local regulation of vascular tone is uncertain. This heterogeneity may be very important in the control of the glomerular filtration rate (GFR) in which the differential tone in the afferent and efferent arterioles is crucial.2. When an endothelium-independent vasodilator, prostacyclin (PGI2) or nitroprusside, was infused into anaesthetized rabbits there were dose-dependent falls in both mean arterial pressure (MAP) and GFR; PGI2 (04 nmol kg-1 min-') altered MAP and GFR by -18 5 + 3-6 % (mean + S.E.M.) and -37-7 + 13-3 % respectively and nitroprusside (30 nmol kg-' min-') by -29 7+3 1% and -67-0+2-4%. In contrast infusion of an endothelium-dependent vasodilator, acetylcholine (ACh) or substance P, produced dose-dependent decreases in MAP but dose-dependent increases in GFR; ACh (10 nmol kg-1 min-) -15 1 + 2 0 % and + 43 8 + 16-5 % and substance P (30 nmol kg-' min-') -187+ 19% and +45-3+231% respectively. The effects of endothelium-dependent and independent vasodilators on GFR was significantly different (p < 0 005). 3. Simultaneous administration of indomethacin, Methylene Blue or NGmonomethyl-L-arginine (L-NMMA), inhibitors of cyclo-oxygenase and endotheliumderived relaxing factor (EDRF) respectively, attenuated or reversed the effect of ACh (10 nmol kg-' min-') on MAP and GFR.4. These data suggest that endothelium-dependent vasodilatation in the kidney has a heterogeneous effect on the renal microvasculature, exerting a preferential effect on afferent glomerular arterioles and thereby preserving GFR despite the fall in MAP. If correct, this has important implications for the regulation of GFR.

Blockade of nitric oxide decreases the renal vasodilatory effect of neuropeptide Y in the insulin-treated diabetic rat

“…ACh may increase renal plasma flow and glomerular filtration rate by vasodilatation of the afferent glomerular arterioles [36]. The vasodilatory effects of ACh on the aorta may be normal [37] or decreased [4] in the diabetic rat.…”

Vascular pharmacology of methylene blue in vitro and in vivo: a comparison with NG‐nitro‐l‐arginine and diphenyleneiodonium

“…Methylene blue potentiated depressor responses to ACh but not nitroglycerin in dogs (Sobey et al, 1988) and potentiated vasodilatation responses to nitrovasodilators and bradykinin in blood perfused dog lungs (Hofman et al, 1992). On the other hand, methylene blue inhibited depressor responses to ACh in rabbits (Cairns et al, 1991), to ACh, adenosine and ATP but not SNP in rats (Loeb & Longnecker, 1992); and to ACh, ATP and SNP but not 8-bromocyclic GMP in lambs (Fineman et al, 1991). Methylene blue did not inhibit the in vivo responses to ACh and SNP in our conscious rats.…”

“…Although ACh-induced vasodilatation is generally believed not to involve prostanoid biosynthesis (Furchgott & Zawadzki, 1980;, there are reports of the attenuation by indomethacin of ACh-induced vasodilatation in vivo (Cairns et al, 1991;Rosenblum et al, 1992). Therefore, the effects of capsaicin and indomethacin on depressor responses to ACh and SNP in vivo were also investigated.…”

Intrarenal haemodynamic and glomerular responses to inhibition of nitric oxide formation in rabbits.

“…Tolins et al 1990;Cairns, Rogerson, Westwick & Neild, 1991), although haemoglobin, which binds NO (Martin, Villani, Jothianandan & Furchgott, 1985), reverses only the efferent arteriolar dilatation to acetylcholine and not the afferent (Loutzenhiser, Hayashi & Epstein, 1990). It has been speculated that endothelium-dependent vasodilators, such as acetylcholine, act on the afferent arteriole via an endothelium-derived factor other than NO (Cairns et al 1991;King & Brenner, 1991). It is also possible that the increase in preglomerular resistance seen in the present study, and in the previous rat studies, may have been partly an autoregulatory response to the increased arterial pressure instead of a direct effect of NO blockade.…”

“…In contrast, *To whom reprint requests should be addressed. Cairns, Rogerson, Westwick & Neild (1991) have argued that NO may predominantly dilate afferent vessels in rabbits, though this conclusion was based on indirect evidence, from experiments in whole kidneys, rather than on direct micropuncture measurements. Clarification of the physiological roles of NO is important because the short half-life of NO makes it 'ideally suited for moment-to-moment modulation' (King & Brenner, 1991) of renal vascular tone, and possibly mesangial tone (Shultz, Schorer & Raij, 1990); that is, to play a major role in the regulation of glomerular ultrafiltration.…”