Sympathetic baroreceptor responses after chronic NG-nitro-L-arginine methyl ester treatment in conscious rats.

Abstract

Blood pressure elevations after nitric oxide inhibition may result in part from increased sympathetic tone. In this study arterial baroreceptor reflex control of heart rate, renal sympathetic nerve activity (RSNA), and adrenal sympathetic nerve activity (ASNA) were compared in rats given normal tap water or a 3.7 nmol/L (10 mg%) solution of jV°-nitro-L-arginine methyl ester (L-NAME) for 1 or 5 weeks. L-NAME raised blood pressure after 5 weeks of treatment (153±3 versus 130±3 and 124±2 mm Hg, 5 weeks versus 1 week and control). The sensitivity of arterial baroreceptor reflex control of RSNA was reduced after both 1 and 5 weeks of treatment (-5.05±0.63% and -4.46±0.2% versus -6.43±0.39% baseline activity per millimeters of mercury). Set point gain of ASNA was attenuated after 5 weeks of I ncreased blood pressure after nitric oxide (NO) blockade may involve the sympathetic nervous system. NO blockade has been shown to increase renal sympathetic nerve activity (RSNA) in anesthetized rats.1 Similarly, microinjection of NO inhibitors in the nucleus tractus solitarius raised RSNA in anesthetized rabbits, 2 and injection of nitroprusside, an NO donor, or the NO synthase substrate L-arginine into vasopressor medullary nuclei decreased RSNA in cats. 3 The presence of NO synthase has been verified in the nucleus tractus solitarius, 4 vasopressor medullary nuclei, 5 spinal intermediolateral nuclei containing preganglionic sympathetic nerve cell bodies, 6 and peripheral sympathetic ganglia, 7 each of which are sites of integration that contribute to arterial baroreceptor reflex (ABR) control of sympathetic tone 8 and thus could be involved in the sympathostimulatory response to NO inhibition. In the present study we examined the effect of chronic NO inhibition with A' G -nitro-L-arginine methyl ester (L-NAME) on ABR control of heart rate, RSNA, and adrenal sympathetic nerve activity (ASNA) in conscious rats. We hypothesized that L-NAME treatment would reduce the sensitivity of baroreceptor reflexes. MethodsMale Sprague-Dawley rats (90 to 110 g) (Ivanovas) were given either normal tap water or an L-NAME solution (3.7 nmol/L [10 From the Franz Volhard Ginic and Max Dclbruck Center for Molecular Medicine, Rudolf Virchow University Hospitals, Free University of Berlin (K.E.S., F.C.L.), and the Department of Internal Medicine -Nephrology, University of Erlangen-Nurnberg (K.E.S., R.V., F.C.L.) (Germany).Correspondence to Friedrich C. Luft, MD, Franz Volhard Clinic, Wiltberg Strasse 50, 13125 Berlin, FRG. treatment compared with controls ( -1 . 7 ± 3 % versus -3.3±3% baseline activity per millimeters of mercury). Maximal inhibition of ASNA was attenuated in groups treated 1 and 5 weeks (60±3% and 66±3% versus 34±4% baseline activity). The maximal increase in both RSNA and ASNA was elevated in rats treated 5 weeks (RSNA: control, 263±19%; 1 week, 224+17%; 5 weeks, 324±20%; ASNA: control, 272±29%; 1 week, 252±31%; 5 weeks, 361±28% baseline activity). The data indicate that chronic L-NAME treatment alters arterial barorecep...

Endothelial Nitric Oxide Gene Knockout Mice

“…32,33 Although we do not have a good explanation for this, we suspect that eNOS may affect the control of baroreflex resetting 34,35 or be involved in establishing the baroreceptor set point. 36 Another possibility is that nNOS expression might be enhanced in eNOS knockout mice as a compensatory mechanism. Increased nNOS activity may have a direct effect on cholinergic receptors and decrease heart rate, because a link between cholinergic receptor stimulation and NOS activation has been reported.…”

eNOS Knockout Mice with Advanced Diabetic Nephropathy Have Less Benefit from Renin-Angiotensin Blockade than from Aldosterone Receptor Antagonists

“…In diabetic eNOSKO mice serum aldosterone levels tended to be lower than that in wild-type diabetic mice, likely because NO deficiency is associated with impairment of sympathetic nervous system. 18,19 However, in contrast, serum aldosterone tended to be paradoxically increased with RAS blockade in eNOSKO mice ( Figure 4H). Mineralocorticoid receptor expression was induced by the diabetic condition in both wild-type and eNOSKO mice ( Table 2).…”

Chronic Nitric Oxide Inhibition Model Six Years On

“…75 These effects may be partly mediated via a reduction in sensitivity of the baroreceptor reflex, which contributes permissively to L-NAME hypertension. 76 In contrast, other investigators have reported evidence that renal nerve traffic plays little or no role in the hypertension of chronic NOS inhibition. 77 The relationship between NO and the SNS is likely to be highly complex, with direct interactions at the various adrenergic receptor subtypes and indirect interactions through baroreceptor control of BP, for example, providing numerous and sometimes opposing influences.…”