Baroreflex Sensitivity in Rabbits During the Development of Experimental Renal Hypertension and Medial Sclerosis

Angell‐James, Jennifer E.; George, M. J.; Peters, C. J.

doi:10.3109/10641968009046427

Cited by 19 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prolonged exposure to high blood pressure is thought to alter baroreceptor reflexes by reducing the distensibility of vessels housing the baroreceptors. 21 However, recent data indicate that 6 weeks of exposure to an L-NAME dose fourfold greater than that used in our study did not alter carotid artery distensibility in Wistar rats. 22 Thus, it is unlikely that the lesser dose and shorter exposure to L-NAME used in the present study produced vascular restructuring that would interfere with appropriate vascular stretch-mediated baroreceptor activation.…”

contrasting

confidence: 50%

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

1994

View full text Add to dashboard Cite

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...

show abstract

contrasting

confidence: 50%

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

1994

View full text Add to dashboard Cite

show abstract

“…Thus, during moderate to heavy exercise in hypertensive subjects, underperfusion of active skeletal muscle, via inherent cardiac dysfunction or impaired peripheral vasodilation, may elicit exaggerated metaboreflex activation. Metaboreflex-induced peripheral vasoconstriction is buffered by the arterial baroreflex (34), and baroreflex function may be impaired in hypertension (3,27,41,55). Thus, enhanced metaboreflex stimulation combined with attenuated baroreflex buffering may allow for exaggerated sympathoactivation during exercise.…”

Section: Discussionmentioning

confidence: 99%

Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension

Sala‐Mercado

Spranger

Abu‐Hamdah

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

-Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 Ϯ 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 Ϯ 2.6 to 141.9 Ϯ 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance. exercise; pressor response; arterial pressure; vasoconstriction; ergoreceptors DYNAMIC EXERCISE elicits workload-dependent increases in sympathetic activity, heart rate (HR), cardiac output (CO), and arterial blood pressure. The increases in arterial blood pressure during exercise may be exaggerated in hypertensive subjects, thereby increasing risk factors for cardiac arrhythmia, infarction, stroke, and sudden cardiac death (5,10,32,49,57). A potential source for the enhanced sympathoactivation in response to exercise in hypertension is the muscle metaboreflex, a powerful pressor response triggered by afferent nerve endings within the active skeletal muscle that respond to the accumulation of metabolites (1,30,39,71). In humans, recent studies support (17, 56) and refute (50) enhanced metaboreflex responsiveness in hypertension. Using a decerebrate rat model, Smith and colleagues (38,43,44,61) concluded that the increases in arterial pressure and renal sympathetic nerve activity in response to stimulation of muscle metaboreceptors are enhanced in spontaneously hypertensive rats (SHR) vs. normotensive (Wistar-Kyoto) controls.Muscle metaboreflex-induced increases in arterial pressure during exercise can occur via increases in CO and/or peripheral vasoconstriction. The relative roles of each of these may be intimately dependent on how the reflex is activated and the contractile abilities of the heart. For example, in heart failure, the ability of the reflex to increase CO is markedly attenuated, yet the peripheral vasoconstrictor responses are enhanced (13,22,33). Further...

show abstract

“…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).…”

Section: Renin-angiotensin-aldosterone Systemmentioning

confidence: 98%

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

Kosugi

Heinig

Nakayama

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

While blockade of the renin angiotensin system (RAS) is beneficial in treating many patients with diabetic nephropathy, some patients show a poor response. We hypothesized that the poor response of RAS blockade is attributed to inability to stimulate endothelial nitric oxide. Recently, we reported that diabetic eNOS knockout (KO) mice develop advanced diabetic nephropathy similar to human disease. Here, we tested the hypothesis that blockade of the RAS would be less beneficial in this model than in diabetic wild-type mice. Both enalapril and telmisartan were less effective at reducing renal injury in diabetic eNOSKO mice compared with diabetic wild-type mice. Blood pressure was only transiently reduced by these treatments in diabetic eNOSKO mice and later returned to levels similar to that of untreated diabetic eNOSKO mice. Serum aldosterone tended to be paradoxically higher with enalapril or telmisartan in diabetic eNOSKO mice, whereas these treatments tended to lower aldosterone in diabetic wild-type mice. The pathogenic role of aldosterone was demonstrated by the evidence that spironolactone significantly reduced blood pressure and prevented renal injury. In addition, a higher dose of enalapril also failed to prevent hypertension and renal injury in diabetic eNOSKO mice. In conclusion , an impaired endothelial NO response could lessen the benefit of RAS inhibition in diabetic renal disease. Aldosterone blockade may provide superior protection in this setting. (Am J Pathol

show abstract

Baroreflex Sensitivity in Rabbits During the Development of Experimental Renal Hypertension and Medial Sclerosis

Cited by 19 publications

References 16 publications

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

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

Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension

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

Contact Info

Product

Resources

About