Baroreflex Buffering and Susceptibility to Vasoactive Drugs

Abstract

Background-The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. Methods and Results-We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 g) increased systolic blood pressure 6Ϯ1.6 mm Hg in control subjects, 6Ϯ1.1 mm Hg in orthostatic intolerance patients, 18Ϯ3.9 mm Hg in patients with essential hypertension, 31Ϯ3.4 mm Hg in patients with monogenic hypertension, and 25Ϯ3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. Conclusions-Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

“…We can also measure the increase in blood pressure produced by the same dose in autonomically blocked subjects ("eNO inhibition" in the equation). Baroreflex restraint can be individually estimated in each subject by taking into account the potentiation of the pressor response to phenylephrine during autonomic blockade compared with baseline 15 (baroreflex restraint). We can, therefore, resolve the unknown component of the equation ("nNO inhibition") to estimate the contribution of nNO to blood pressure regulation (see Results for further explanation).…”

“…The potentiation of the pressor effects of phenylephrine observed after autonomic blockade estimates the magnitude of baroreflex buffering 15 and can be used to predict how much blood pressure should have increased if only the baroreflex was removed. An example is given in Figure 3.…”

Women Have Lower Tonic Autonomic Support of Arterial Blood Pressure and Less Effective Baroreflex Buffering Than Men

“…The ability of baroreflexes to "buffer" acute changes in BP under such conditions (ie, baroreflex buffering [BRB]) is reduced in certain physiological 9 and disease 10 states associated with impaired short-term BP regulation and/or altered responsiveness to vasoactive medications. In light of previous reports of less effective short-term regulation of BP in women than in men, 1,2,6,[11][12][13][14] we also hypothesized that premenopausal women have lower BRB of BP than men of similar age.…”

Short-term Aerobic Exercise Reduces Nitroglycerin-induced Orthostatic Intolerance in Older Adults With Type 2 Diabetes

“…Impaired arterial baroreflex function has been shown to be predictive of poor tolerability of vasodilatory medications in older adults 4 suggesting that improving arterial baroreflex sensitivity with exercise 5 could potentially improve orthostatic tolerance to GTN in this vulnerable population. Vigorous aerobic training has been shown to improve orthostatic tolerance in young normal subjects, 6 but some investigations have demonstrated a worsening [7][8][9] or no 10 effect of aerobic training on orthostatic tolerance.…”