Chronic angiotensin II infusion attenuates the renal sympathoinhibitory response to acute volume expansion

Abstract

In this study the hypothesis was tested that chronic infusion of ANG II attenuates acute volume expansion (VE)-induced inhibition of renal sympathetic nerve activity (SNA). Rats received intravenous infusion of either vehicle or ANG II (12 ng·kg −1 ·min −1 ) for 7 days. ANG II-infused animals displayed an increased contribution of SNA to the maintenance of mean arterial pressure (MAP) as indicated by ganglionic blockade, which produced a significantly (P < 0.01) greater decrease in MAP (75 ± 3 mmHg) than was observed in vehicle-infused (47 ± 8 mmHg) controls. Rats were then anesthetized, and changes in MAP, mean right atrial pressure (MRAP), heart rate (HR), and renal SNA were recorded in response to right atrial infusion of isotonic saline (20% estimated blood volume in 5 min). Baseline MAP, HR, and hematocrit were not different between groups. Likewise, MAP was unchanged by acute VE in vehicle-infused animals, whereas VE induced a significant bradycardia (P < 0.05) and increase in MRAP (P < 0.05). MAP, MRAP, and HR responses to VE were not statistically different between animals infused with vehicle vs. ANG II. In contrast, VE significantly (P < 0.001) reduced renal SNA by 33.5 ± 8% in vehicle-infused animals but was without effect on renal SNA in those infused chronically with ANG II. Acutely administered losartan (3 mg/kg iv) restored VEinduced inhibition of renal SNA (P < 0.001) in rats chronically infused with ANG II. In contrast, this treatment had no effect in the vehicle-infused group. Therefore, it appears that chronic infusion of ANG II can attenuate VE-induced renal sympathoinhibition through a mechanism requiring AT 1 receptor activation. The attenuated sympathoinhibitory response to VE in ANG II-infused animals remained after arterial barodenervation and systemic vasopressin V 1 receptor antagonism and appeared to depend on ANG II being chronically increased because ANG II given acutely had no effect on VE-induced renal sympathoinhibition. Keywordssympathetic nerve activity; cardiopulmonary reflex; body fluid balance; arterial baroreceptor reflex Numerous studies have investigated interactions between circulating ANG II and the arterial baroreceptor reflex. Whereas recent studies indicate that an acute increase in circulating ANG II can attenuate the increase in sympathetic nerve activity (SNA) that follows arterial baroreceptor unloading (34), chronic increases of ANG II have been repeatedly demonstrated to reset arterial baroreflex control of SNA (4, 6). The latter effect may permit SNA to rise relative to the prevailing level of arterial pressure. In addition to the arterial Copyright © 2003 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript baroreflex, the cardiopulmonary baroreflex is also an important determinant of sympathetic outflow as well as sodium and water balance. However, the extent to which chronic increases of ANG II might interact with this reflex to modify the SNA response to volume expansion (VE) is not known. This is surprising given that norma...

Effect of Intravenous Angiotensin II Infusion on Responses to Hypothalamic PVN Injection of Bicuculline

“…Although MAP was unchanged throughout the infusion protocol in vehicle-treated control rats, it increased after urethane/␣-chloralose anesthesia, as reported previously. 17 Nevertheless, responses to BMI injected in the PVN in vehicle-infused animals were similar to those reported in previous studies. 4 -6 It is important to note that anesthesia did not affect the elevated MAP produced by continuous Ang II infusion.…”

“…Moreover, effects of aldosterone do not appear to contribute significantly to the findings of the current study, since values of plasma aldosterone return toward baseline within 48 hours during continuous infusion of Ang II. 27 Acute and long-term Ang II treatments are well known to differentially modulate SNA and arterial pressure through both peripheral 28 and central 17,29 actions. In the current study, 7-day peripheral Ang II infusion produced a significant and sustained increase in MAP.…”

“…Standard methods were used to record renal SNA. 4,17 Renal SNA responses to intravenous sodium nitroprusside and phenylephrine were used to assess the signal-to-noise ratio of each recording. Hematocrit was measured from venous blood.…”

“…The vena cava was catheterized to infuse Ang II or vehicle. 17 After regaining consciousness, a solution of D5W and ampicillin (28 mg/24 h) was infused (5.7 mL/24 h) continuously for 5 days. Rats were then separated into two groups; one received fresh Ang II (12 ng/kg per minute) in the infusate daily and the other (control group) was maintained on the vehicle infusion for the final 7 days.…”

“…9,10 Neurons in two forebrain CVOs, the subfornical organ and organum vasculosum of the lamina terminalis, express Ang II AT 1 receptors in high density 11 and appear to sense and respond to circulating Ang II. 9,[12][13][14][15] Although Ang II increases SNA through these and other central actions, 16,17 the mechanism by which circulating Ang II enhances PVN neuronal excitability is not fully understood.…”