Influence of Prolonged Baroreflex Activation on Arterial Pressure in Angiotensin Hypertension

Abstract

Abstract-Despite recent evidence indicating sustained activation of the baroreflex during chronic infusion of angiotensin II (Ang II), sinoaortic denervation does not exacerbate the severity of the hypertension. Therefore, to determine whether Ang II hypertension is relatively resistant to the blood pressure-lowering effects of the baroreflex, the carotid baroreflex was electrically activated bilaterally for 7 days in 5 dogs both in the presence and absence of a continuous infusion of Ang II (5 ng/kg per minute) producing high physiological plasma levels of the peptide. Under control conditions, basal values for mean arterial pressure (MAP) and plasma norepinephrine concentration (NE) were 93Ϯ1 mm Hg and 99Ϯ25 pg/mL, respectively. By day 7 of baroreflex activation, MAP and NE were reduced to 72Ϯ4 mm Hg (Ϫ21Ϯ3 mm Hg) and 56Ϯ15 pg/mL, respectively, but PRA was unchanged (controlϭ0.41Ϯ0.06 ng ANG I/mL per hour). All values returned to basal levels by the end of a 7-day recovery period. After 7 days of Ang II infusion, MAP increased from 93Ϯ3 to 129Ϯ3 mm Hg, whereas NE fell from 117Ϯ15 to 86Ϯ23 pg/mL. During the next 7 days of baroreflex activation/Ang II infusion, further reductions in NE were not statistically significant, and on the final day of baroreflex activation, the reduction in MAP was only 5Ϯ1 mm Hg, compared with 21Ϯ3 mm Hg in the control normotensive state.

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

“…The corresponding values after renal denervation (2.1Ϯ0.2 ng/dL and 1.5Ϯ0.3 g/dL) were not significantly different from the above. As in previous studies, 6,10 in neither group was there significant changes in the plasma levels of these steroids during baroreflex activation. Because of an insufficient amount of plasma, plasma cortisol concentration was measured in only 3 of the 6 dogs.…”

“…As expected from previous studies, prolonged activation of the baroreflex produced sustained decreases in sympathetic activity (plasma NE concentration) and arterial pressure. 6,10 In addition, before renal denervation, these responses were associated with a fall in PRA, presumably reflecting the effects of reflex-induced renal sympathoinhibition on renin release. 13,14 Although baroreflex-mediated suppression of renal sympathetic nerve activity inhibits renin secretion, this could not possibly account for the failure of PRA to increase significantly in response to reductions in arterial pressure during baroreflex activation in denervated kidneys.…”

“…6,10 In association with the modest retention of sodium (Figure 3), there were small (5% to 10%), but nevertheless significant, reductions in both hematocrit (controlϭ0.39Ϯ0.03 g/dL) and plasma protein (controlϭ6.1Ϯ0.2 g/dL) concentration during baroreflex activation. As reported previously, 6 these changes in hematocrit and plasma protein concentration were achieved by day 1 of baroreflex activation.…”

“…[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.…”

“…6,10 To activate the carotid baroreflex, an externally adjustable pulse generator is used to electrically stimulate electrodes chronically implanted around both carotid sinuses of dogs. With this methodology, one can achieve sustained and controllable reductions in mean arterial pressure (MAP) that are associated with distinct reductions in circulating levels of norepinephrine (NE), indicating inhibition of sympathetic activity.…”