Importance of the renal nerves in established two-kidney, one clip Goldblatt hypertension.

Abstract

SUMMARY Increased sympathetic nervous system activity has been demonstrated in established twokidney, one clip hypertension in the rat. To determine the importance of the renal nerves in this model of hypertension, renal denervation of the clipped kidney (n = IS), renal denotation of the nondlpped kidney (n = 14), sham operation (n = 20), or undlpping (n = 12) was carried out 6 weeks after the onset of two-kidney, one clip hypertension. Nortnotensive age-and sex-matched rats were used as controls (n » 10). Sham operation or renal denerration of the nonclipped kidney produced no change in systolic Mood pressure while renal denervation of the clipped kidney resulted in a significant decrease in systolic blood pressure (195 ± 7 to 150 ± 6 mm Hg; p < 0.01). Unclipping lowered systolic Mood pressure to normotensive levels (126 ± 5 mm Hg). Eight days after operation, plasma norepinephrine and mean arterial pressure before and after ganglionic blockade with 30 mg/kg hexamethonium bromide were measured in conscious unrestrained resting animals as indices of peripheral sympathetic nervous system activity. Plasma norepinephrine was significantly higher in hypertensive sham-operated rats (347 ± 26 pg/ml) and nondipped-kidney denervated rats (355 ± 27 pg/ml) compared to nonnotensive controls (228 ± 22 pg/ml) (p < 0.01). Both renal denervation of the clipped kidney and unclipping restored plasma norepinephrine to normal levels (215 ± 16 and 232 ± 19 pg/ml, respectively). Ganglionic blockade in hypertensive sham-operated and nondipped-kidney denervated animals resulted in a significantly greater decrease in mean arterial pressure than that which occurred in clipped-kidney denervated, undipped, or control rats. There was no difference in plasma renln activity, dipped-kidney renln activity, or blood pressure response to 250 fig SQ 20,881 administration among sham-operated, dipped-kidney deoervated, or nondipped-kidney denervated animals. The data indicate that the depressor effect of dipped kidney denervation or undipping in the two-kidney, one dip hypertensive rat is associated with a decrease in sympathetic nervous system activity. These results support the hypothesis that the afferent renal nerves contribute to the maintenance of hypertension in this model by modulating the activity of the sympathetic nervous system. giotensin system has been implicated in the initial hypertensive response to clipping of the renal artery in a one-kidney or twokidney rat, the renin-angiotensin system appears to play a diminishing role as hypertension becomes established in these models. evidence suggesting participation of the sympathetic nervous system in the maintenance of these forms of renal hypertension.*"* Since increases in efferent renal sympathetic nerve activity facilitate the retention of sodium and result in renin release, we previously studied the effect of renal denervation in the onekidney renal hypertensive rat at a time when increased peripheral sympathetic nervous system activity was present. We found that renal denervation ...

Angiotensin AT1receptors in paraventricular nucleus contribute to sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats

“…Sympathetic activity is enhanced in patients with essential hypertension and secondary hypertension (Vecchione et al 2000;Neumann et al 2007;Lambert et al 2007;Fisher & Fadel, 2010) and in various experimental hypertensive models (Katholi et al 1982;Fujita et al 2007;Stocker et al 2007;Tan et al 2010). The overactive sympathetic outflow contributes to the pathogenesis of hypertension and the progression of organ damage (Mancia et al 1999;Rahn et al 1999;Morise et al 2000;Grisk, 2005).…”

“…Sympathetic activity is enhanced in various hypertensive animal models, such as spontaneously hypertensive rats (Tan et al 2010), renovascular hypertensive rats (Katholi et al 1982), obesity-related hypertensive rats (Stocker et al 2007) and deoxycorticosterone acetatesalt hypertensive rats (Yemane et al 2010). The enhanced sympathetic outflow is also found in patients with essential hypertension (Fisher & Fadel, 2010) and secondary hypertension, such as in chronic kidney disease (Neumann et al 2007), obesity (Lambert et al 2007) and diabetes (Vecchione et al 2000).…”

The role of oxidative stress in renovascular hypertension

“…52 Several lines of evidence suggest that increased activity in afferents from diseased kidneys can act to increase sympathetic nerve activity and hypertension. [53][54][55] Indeed, ablation to excise renal nerves that carry both efferent sympathetic and afferent sensory fibers reduced blood pressure and renal norepinephrine spillover in patients with essential hypertension resistant to pharmacological treatment. 56 Chronic renal hypoxia has been considered an underlying cause of progressive chronic kidney disease; therefore, our hypothesis is that the renal vasoconstriction and hypoxia induced by oxidative stress in the diseased kidney might be a mechanism that increases sympathetic vasomotor tone with renovascular hypertension.…”

Diminished A‐type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats

“…Elevated sympathetic outflow is known to contribute to the development and/or maintenance of hypertension, and is commonly observed in various forms of hypertensive disorders (Judy et al 1976;Esler & Kaye, 1998;Guyenet, 2006), including those with a renovascular origin (Katholi et al 1982;Oparil et al 1987;Bergamaschi et al 1995). While the initial phase of renovascular hypertension is primarily due to overactivation of the renin-angiontensin system (RAS), maintenance of high blood pressure at more established, chronic stages of the disease involves activation of neurogenic pressor mechanisms, including sustained sympathoexcitation (Martinez-Maldonado, 1991;Bergamaschi et al 1995;Fink, 1997).…”