Differentiated Response of the Sympathetic Nervous System to Angiotensin-Converting Enzyme Inhibition in Hypertension (original) (raw)
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Sympathetic and Renin–Angiotensin Activity in the Pathophysiology of Hypertension
The implication of the sympathetic nervous system (SNS) in the pathogenesis of essential hypertension has been suggested a long time ago, considering the major role played by this system in blood pressure (BP) regulation. Studies based on both global (e.g., plasma norepinephrine) and regional (norepinephrine spillover and microneurography) assessments of sympathetic activity have demonstrated that neurogenic mechanisms may be involved in up to 50 % of all cases of essential hypertension. In addition, renal sympathetic denervation has been shown to induce signifi cant and persistent decreases in BP. Moreover, there is evidence that sympathetic hyperactivity may contribute directly to target-organ damage, including cardiac hypertrophy, vascular remodeling, and renal dysfunction. The specifi c causes of sympathetic activation in essential hypertension are not entirely known, but genetic factors, high dietary salt intake, as well as several metabolic and neurohumoral abnormalities have been involved. In patients with obesity-and metabolic syndrome-associated hypertension, SNS overactivity may result from many factors, including hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, hypoghrelinemia, and RAAS activation.
Autonomic and Autacoid Pharmacology, 2009
The various interactions between the renin-angiotensin system and the sympathetic system have been established at different levels and have been shown to bear prominent pathophysiological implications. This study was undertaken to characterize the renal responses to acute unilateral renal denervation of the left kidney in anaesthetized Wistar-Kyoto rats (WKY) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to renal nerve stimulation (RNS). Twenty-four male WKY rats underwent acute unilateral renal denervation. After 7 days treatment with losartan, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The renal nerves were directly stimulated at a sequence of frequencies of 1, 2, 4, 6, 8, and 10 Hz at 0.2 ms duration and 15V for a period of 15 seconds in ascending and descending manner. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation. The data showed that there was significantly (all P<0.05) decreased renal vascular responsiveness to neural stimuli in denervated rats compared to those with intact renal nerves. In losartan treated denervated WKY rats, there were significant (all P<0.05) reductions in the renal vasoconstrictor responses to neural stimuli as compared to that of untreated denervated WKY rats. These data also suggested a possible interaction between sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in terms of a crosstalk relationship between renal AT 1 and 1 α -adrenoceptor subtypes in the renal vasculature of normal rats.
2009
The various interactions between the renin-angiotensin system and the sympathetic system have been established at different levels and have been shown to bear prominent pathophysiological implications. This study was undertaken to characterize the renal responses to acute unilateral renal denervation of the left kidney in anaesthetized Wistar-Kyoto rats (WKY) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to renal nerve stimulation (RNS). Twenty-four male WKY rats underwent acute unilateral renal denervation. After 7 days treatment with losartan, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The renal nerves were directly stimulated at a sequence of frequencies of 1, 2, 4, 6, 8, and 10 Hz at 0.2 ms duration and 15V for a period of 15 seconds in ascending and descending manner. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation. The data showed that there was significantly (all P<0.05) decreased renal vascular responsiveness to neural stimuli in denervated rats compared to those with intact renal nerves. In losartan treated denervated WKY rats, there were significant (all P<0.05) reductions in the renal vasoconstrictor responses to neural stimuli as compared to that of untreated denervated WKY rats. These data also suggested a possible interaction between sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in terms of a crosstalk relationship between renal AT 1 and 1 α -adrenoceptor subtypes in the renal vasculature of normal rats.
Local Renin-Angiotensin System in Sympathetic Overactivity of Spontaneously Hypertensive Rats
Hypertension Research, 1996
The present study was designed to clarify whether modulation of norepinephrine (NE) release by vascular angiotensin (Ang) II is involved in the increased peripheral sympathetic activity of spontaneously hypertensive rats (SHR). In the perfusion system of isolated mesenteric vascular beds, periarterial nerve stimulation (PNS)-evoked NE overflow was significantly greater in SHR than Wistar-Kyoto rats (WKY). Administration of Ang II increased PNS-induced NE overflow, which could be reversed by pretreatment with the AT1 receptor antagonist CV-11974 in both types of rats; the facilitation by Ang II was more potent in SHR. Moreover, CV-11974 by itself could attenuate PNS-evoked NE overflow, the extent of which was also significantly greater in SHR, suggesting an augmented sympatho-facilitatory effect of enodogenous Ang II in SHR. Consistently, sympatho-facilitation by Ang I, which could be abolished by the angiotensin converting enzyme (ACE) inhibitor imidaprilat, was apparently greater than that of Ang II in SHR, despite no difference in WKY. These findings suggest that the increased peripheral sympathetic activity in SHR is attributed not only to the elevated sensitivity of nerve endings to Ang II but also to the increased local generation of Ang II, an effect possibly mediated by augmented vascular ACE activity.
Sympathetic Renal Innervation and Resistant Hypertension
2011
Hypertension in chronic renal disease and renovascular disease is often resistant to therapy. Understanding the pathogenic mechanisms responsible for hypertension in these conditions may lead to improved and more targeted therapeutic interventions. Several factors have been implicated in the pathogenesis of hypertension associated with renal disease and/or renal failure. Although the role of sodium retention, total body volume expansion, and hyperactivity of the renin-angiotensin-aldosterone system (RAAS) are well recognized, increasing evidence suggests that afferent impulses from the injured kidney may increase sympathetic nervous system activity in areas of the brain involved in noradrenergic regulation of blood pressure and contribute to the development and maintenance of hypertension associated with kidney disease. Recognition of this important pathogenic factor suggests that antiadrenergic drugs should be an essential component to the management of hypertension in patients with kidney disease, particularly those who are resistant to other modalities of therapy.