Mechanisms regulating glomerular hemodynamics

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Renal hemodynamics play an important role in the pathophysiology of hypertension and progressive renal dysfunction. The juxtaglomerular apparatus, composed of glomerular afferent and efferent arterioles and the macula densa, regulates the glomerular hemodynamics. It has recently been shown that nitric oxide (NO), adenosine (Ado) and the cytochrome P450 metabolites of arachidonic acid (20-HETE and EET) plays an important modulatory role in the JGA function. In this study, in order to examine the function of the JGA directly, we employed preparations of isolated microperfused afferent arterioles with or without attached macula densa perfused. Result are as follow.1)When the NaCl concentration of the macula densa perfusate was increased, the afferent arteriole exhibited constriction, the phenomenon called TGF, this response was abolished by pretreatment with Ado Al receptor. On the other hand, administration of a low dose of Ado into the afferent ceteriolar but not macula densa perfusate … More augmented the TGF-induced constriction. These results suggest that Ado and its Al receptor are essential to the signal augmented the TGF-induced constriction. These results suggest that Ado and its Al receptor are essential to the signal transmission of TGF, and the site of action seems to be the JGA interstitium/vascularture but not the tubular lumen.2)When reuronal nitric oxide synthase (nNOS) in the macula densa was inhibited acutely, afferent arteriolar constriction-induced by TGF was augmented, while in nNOS knockout mice, TGF remained unaltered, possibly due to some unknown adaptation mechanisms. In addition, results suggest that during a low sodium intake, the macula densa NO production is enhanced, thereby opposing the vasoconstrictor action of angiotensin ll (All) and maintaining renal blood flow.3)The All-induced vasoconstriction of microperfused afferent arterioles was augmented by blockade of EET synthesis. This effect was abolished by blocking AT2 receptors, suggesting that All stimulates synthesis of the vasodilator EET via AT2 receptors.4)ACE inhibitors induced cytochrome P450 enzyme expression and thereby enhance synthesis of 20-HETE and EET in microsome fractions of the kidney. This enhancement seems to be mediated by ACE inhibitor-induced elevation of tissue kinin levels. Thus, the present study clarifies, in part, the role of NO,Ado,20-HETE and EE in the regulation of TGA function. Less