Hypertension induced by nitric oxide synthesis inhibition is renal nerve dependent.

Abstract

Recent studies have indicated that chronic administration of iV"-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, produces marked hypertension. Although the mechanism of this form of hypertension is not well understood, several studies have demonstrated that sympathetic nerve activity is at least acutely elevated after L-NAME administration. To evaluate the potential role of the renal sympathetic nerves in L-NAMEinduced hypertension, we compared the blood pressure response to L-NAME in four groups of Sprague-Dawley rats (n=8 each): (1) sham-operated vehicle-treated, (2) shamoperated L-NAME-treated, (3) denervated vehicle-treated, and (4) denervated L-NAME-treated. After renal denervation or sham surgery, L-NAME was added to the drinking N itric oxide (NO) is now known to be an important participant in a variety of physiological processes, including several that influence arterial pressure.1 Acute administration of substituted arginine analogues that inhibit NO synthesis, including /V°'-nitro-Larginine methyl ester (L-NAME), results in a prompt increase in arterial pressure.2 -3 The immediate increase in arterial pressure may be principally due to an increased vascular smooth muscle tone as a consequence of decreased endothelial synthesis of NO. Increases in sympathetic nerve activity have been described after acute NO synthesis inhibition, 46 suggesting that neurogenic mechanisms may also contribute to the acute increase in arterial pressure.Several laboratories have recently reported that continued administration of inhibitors of NO synthesis induces a sustained hypertension.79 Although a precise mechanism by which continued NO synthesis inhibition may induce chronic hypertension remains to be identified, renal control of fluid and electrolyte balance is thought to play a dominant role in the long-term control of arterial pressure in both normal and pathophysiological states.10 ' 11 Renal sympathetic nerve activity is known to be increased at least acutely after administration of NO synthesis inhibitor, 46 and activation of the renal sympathetic nerves is known to inhibit renal sodium excretion and promote renal renin secretion. 12 Thus, we hypothesized that chronic L-NAME-induced hypertension may be, in part, the result of a sustained activation of the renal sympathetic nerves and the resultant resetting of renal fluid and electrolyte balance water (70 rngVlOO mL) for 4 weeks, and arterial pressure was measured weekly by the tail-cuff method. L-NAME treatment caused a progressive increase in arterial pressure in shamoperated rats, rising to 154±6 mm Hg by week 4 of treatment compared with 115±2 mm Hg in the vehicle-treated shamoperated group (P<.005). In contrast, the development of hypertension was significantly delayed and attenuated in renaldenervated rats treated with L-NAME. The results of our study suggest that L-NAME-induced hypertension may be partly mediated by or is at least dependent on the integrity of the renal nerves. Key Words • blood pressure • end...

Renal Nerve-Mediated Erythropoietin Release Confers Cardioprotection During Remote Ischemic Preconditioning

“…These vessels were then painted with a solution of 10% phenol in ethanol through a midline abdominal incision. 30 Sham-operated control mice received only a midline incision, and the renal nerves were left intact. At the end of the experiment, renal denervation was verified by analyzing the renal norepinephrine content in the kidney.…”

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Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

“…The long-term control of arterial pressure is thought to be regulated by the renal control of fluid and electrolyte balance (15), and evidence has accumulated suggesting that renal sodium excretion is impaired, at least in part, via a renal sympathetic nerve action (16). Renal denervation has been documented to delay the onset and attenuate the severity of some forms of hypertension of different pathogenesis (13,17). The significance of the present results is that they support an important role for renal sympathetic nerve activity in hypertension induced by DOCA and salt overload, as shown previously (18).…”

Evidence for a critical role of nitric oxide in the tonic excitation of rabbit renal sympathetic preganglionic neurones.

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