Baroreceptor Denervation Prevents Sympathoinhibition During Angiotensin II–Induced Hypertension

Abstract

Abstract-Arterial baroreflexes are well established to provide the basis for short-term control of arterial pressure;however, their role in long-term pressure control is more controversial. We proposed that if the sustained decrease in renal sympathetic nerve activity (RSNA) we observed previously in response to angiotensin II-induced hypertension is baroreflex mediated, then the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. Arterial pressure and RSNA were recorded continuously via telemetry in sham and SAD rabbits living in their home cages before, during, and after a 7-day infusion of angiotensin II (50 ng ⅐ kg Ϫ1 ⅐ min Ϫ1). The arterial pressure responses in the 2 groups of rabbits were not significantly different (82Ϯ3 mm Hg sham versus 83Ϯ3 mm Hg SAD before angiotensin II infusion, and 101Ϯ6 mm Hg sham versus 100Ϯ4 mm Hg SAD day 6 of angiotensin II). In sham rabbits, there was a significant sustained decrease in RSNA (53Ϯ7% of baseline on day 2 and 65Ϯ7% on day 6 of the angiotensin II). On ceasing the angiotensin II, all variables recovered to baseline. In contrast, RSNA did not change in SAD rabbits with the angiotensin II infusion (RSNA was 98Ϯ8% of baseline on day 2 and 98Ϯ8% on day 6 of the angiotensin II infusion). These results support our hypothesis that the reduction in RSNA in response to a pressor dose of angiotensin II is dependent on an intact arterial baroreflex pathway. Key Words: baroreceptors Ⅲ denervation Ⅲ rabbits Ⅲ nervous system, sympathetic renal A rterial baroreflexes are well established to provide the basis for the short-term control of arterial pressure; however, it has generally been accepted that they do not regulate long-term pressure. 1 This concept is based on 3 main lines of evidence, the first being that arterial baroreceptors reset during sustained increases in arterial pressure. 2 Second, chronic sinoaortic denervation, while producing tremendous lability in arterial pressure, does not result in higher average 24-hour pressures. 3 Finally, it is thought that the reflex gain of the baroreceptor control system is not sufficiently strong to explain the long-term constancy of arterial pressure. 4 However, a number of recent experiments have renewed interest in the role of the baroreflex in long-term arterial pressure control and suggest that arterial baroreflexes may act chronically to suppress sympathetic nerve activity. Lohmeier et al 5 studied responses to 5 days of angiotensin II infusion in dogs using a split-bladder preparation combined with denervation of 1 kidney. During angiotensin II infusion, sodium excretion from the innervated kidney significantly increased compared with the denervated kidney, indicating a decrease in renal sympathetic nerve activity (RSNA). The sustained increase in sodium excretion from the innervated kidney was proposed to be mediated by a sustained baroreflex-mediated suppression of RSNA because after cardiopulmonary and sinoaortic denervation, the sodium excretion from the innervated kid...

Time-dependent changes in autonomic control of splanchnic vascular resistance and heart rate in ANG II-salt hypertension

“…It is clear, however, that baseline HR is initially suppressed during ANG II-induced hypertension, as shown by the tachycardic response to ganglionic blockade on day 3 of ANG II in HS rats. This initial decrease in sympathetic tone (and/or increase in parasympathetic tone) to the heart is likely baroreflex mediated, which is consistent with previous studies showing that renal SNA is initially suppressed during ANG II-induced hypertension in a baroreflex-dependent manner (1,17). Suppression of activity is not seen with sympathetic effects on splanchnic resistance arteries and lumbar SNA (28), suggesting that there is a region-specific difference in the degree of baroreceptor inhibition of sympathetic tone in response to the initial phase of ANG II hypertension.…”

“…Assessment of autonomic control of MAP, heart rate (HR), and mesenteric vascular resistance (MVR) during ANG II infusion was performed by ganglionic blockade on days 1,3,5,7,10, and 13 of ANG II and compared with values obtained on the 3rd day of control and 4th day of recovery. Ganglionic blockade was achieved by intravenous administration of hexamethonium (H0879; Sigma-Aldrich, St. Louis, MO) at a dose of 20 mg/kg (23).…”

“…Suppression of renal SNA has also been directly measured during ANG II-induced hypertension in rabbits (2) and indirectly in dogs (4), suggesting that this suppression is not a salt-dependent effect, per se, but rather a baroreceptor-mediated phenomenon. Indeed, the chronic ANG II-induced decrease in renal SNA is not observed in sinoaortic-denervated animals (17,1). Additionally, ANG II-induced hypertension is unaffected by sinoaortic denervation, suggesting that baroreflex-mediated effects on renal SNA are not critical to the development of hypertension.…”

“…Mean arterial pressure (MAP), heart rate (HR), superior mesenteric artery blood flow, and mesenteric vascular resistance (MVR) were measured during 4 control days, 14 days of ANG II delivered subcutaneously (150 ng · kg Ϫ1 · min Ϫ1 ), and 4 days of recovery in conscious rats fed a HS (2% NaCl) or low-salt (LS; 0.1% NaCl) diet. Autonomic effects on MAP, HR, and MVR were assessed by acute ganglionic blockade with hexamethonium (20 mg/kg iv) on day 3 of control, days 1,3,5,7,10, and 13 of ANG II, and day 4 of recovery. MVR increased during ANG II infusion in HS and LS rats but remained elevated only in HS rats.…”

Renal Denervation Does Not Abolish Sustained Baroreflex-Mediated Reductions in Arterial Pressure

“…[1][2][3][4][5][6][7][8][9][10] These studies, conducted over several weeks, indicate that baroreflex resetting is incomplete in experimental models of hypertension. They also indicate that during chronic increases in arterial pressure, there is sustained baroreflex-mediated suppression of renal sympathetic nerve activity and attendant increments in renal excretory function, responses expected to attenuate the severity of hypertension.…”