Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(-1). min(-1). In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.

Abstract-Recent studies indicate that renal sympathetic nerve activity is chronically suppressed in angiotensin (Ang II) hypertension and that baroreflexes play a critical role in mediating this response. To support these findings, we determined whether the hypertension associated with chronic infusion of Ang II at 4.8 pmol/kg per minute (5ng/kg per minute) produces sustained activation of medullary neurons that participate in the central baroreceptor reflex pathway. We used Fos-like (Fos-Li) protein immunohistochemical methods to determine activation of neurons in the nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM). Results were compared in three groups of chronically instrumented dogs subjected to infusion of: 1) saline (control); 2) Ang II-2 hours (acute); and 3) Ang II-5 days (chronic here has been a long-standing interest in the mechanisms that contribute to the hypertension induced by pathophysiological levels of angiotensin (Ang II) in the circulation. Although circulating Ang II has sustained actions on the kidneys, vasculature, and adrenal glands that promote chronic hypertension, acute studies have also demonstrated that circulating Ang II can act in the central nervous system to increase sympathetic activity and arterial pressure. 1 However, the relevance of these acute studies to the pathophysiological role of Ang II in hypertension has not been settled. In large part, this is because of technical limitations that prevent determination of both the long-term changes in sympathetic activity and the sustained influence of the sympathetic nervous system on renal excretory function.It is well established that the kidneys play a critical role in the long-term regulation of arterial pressure. 2 The few studies that have determined the temporal changes in renal sympathetic nerve activity and the resultant neurally-induced renal excretory responses during chronic Ang II infusion strongly indicate interactions between the renin-angiotensin and sympathetic nervous systems in the genesis of the hypertension. [3][4][5][6][7] In direct opposition to the notion that the sympathetic nervous system contributes to Ang II hypertension, these studies indicate that suppression of renal sympathetic nerve activity and attendant increases in sodium excretion are sustained responses in Ang II hypertension. 3-7 These findings therefore suggest that the sympathetic nervous system actually attenuates rather than contributes to the severity of Ang II hypertension. Furthermore, based on a recent study in chronically instrumented dogs, it seems that chronic renal sympathoinhibition in Ang II hypertension is mediated by baroreflexes. 6 As it is well established that baroreceptors undergo rapid adaptation and resetting, 8 this recent study is rather surprising. In fact, the implication of this study is that the baroreflex does not completely reset in chronic hypertension and, therefore, may play a role in the chronic regulation of arterial pressure. The primary object...

Recent studies indicate that baroreflex suppression of renal sympathetic nerve activity is sustained for up to 5 days of ANG II infusion; however, steady-state conditions are not associated with ANG II hypertension of this short duration. Thus the major goal of this study was to determine whether neurally induced increments in renal excretory function during chronic intravenous infusion of ANG II are sustained under more chronic conditions when hypertension is stable and sodium balance is achieved. Experiments were conducted in five conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. ANG II was infused after control measurements for 10 days at a rate of 5 ng. kg(-1). min(-1). Twenty-four-hour control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 92 +/- 4 mmHg and 0.99 +/- 0.05, respectively. On days 8-10 of ANG II infusion, MAP was stable (+30 +/- 3 mmHg) and sodium balance was achieved. Whereas equal amounts of sodium were excreted from the kidneys during the control period, throughout ANG II infusion there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 10 Den/Inn sodium = 0.56 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. The greater rate of sodium excretion in Inn vs. Den kidneys during renal sympathoinhibition also revealed a latent impairment in sodium excretion from Den kidneys. Although the Den/Inn for sodium and the major metabolites of nitric oxide (NO) decreased in parallel during ANG II hypertension, the Den/Inn for cGMP, a second messenger of NO, remained at control levels throughout this study. This disparity fails to support the notion that a deficiency in NO production and action in Den kidneys accounts for the impaired sodium excretion. Most importantly, these results support the contention that baroreflex suppression of renal sympathetic nerve activity is sustained during chronic ANG II hypertension, a response that may play an important role in attenuating the rise in arterial pressure.

14 Recent studies indicate that renal sympathetic nerve activity is chronically supressed during angiotensin (ANG II) hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in 5 conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (DEN) and innervated (INN) kidneys. Dogs were studied before and after deafferentation of cardiopulmonary receptors and arterial baroreceptors (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng/kg/min; this was followed by a 5-day recovery period. In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from DEN and INN kidneys (DEN/INN) were 98±4 mm Hg and 1.04±0.04 respectively. As expected, sodium retention occurred for several days during ANG II infusion before sodium balance was achieved at an increase in MAP of 30-35 mm Hg. Throughout ANG II infusion, there was a substantially greater rate of sodium excretion from INN versus DEN kidneys (day 5 DEN/INN-sodium = 0.51±0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD + SAD did not influence baseline values for either MAP or the DEN/INN-sodium, nor did it alter the severity of ANG II hypertension. However, after CPD + SAD there was an appreciably lower, rather than a greater, rate of sodium excretion from INN versus DEN kidneys during ANG II hypertension (day 5 DEN/INN-sodium = 2.02±0.14). These data indicate that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects that promote sodium retention.