Cardiovascular counterregulation during sympathetic inhibition in normal subjects and patients with mild hypertension.

Abstract

SUMMARY The influence of agents that inhibit sympathetic nerve activity on cardiovascular responsiveness as related to major pressor factors has been unclear. Therefore, these components were evaluated in 11 normal subjects and 13 patients with mild essential hypertension before and after 4 weeks of sympathetic neuron blockade with the agent debrisoquine. In these normal and mildly hypertensive subjects, sympathetic neuron blockade caused approximately similar decreases in urinary and supine or upright plasma norepinephrine (NE) levels (average changes in the two groups, -4 1 % and -45%, respectively; p < 0.05 to < 0.005), the chronotropic dose of isoproterenol ( -45% and -38%), and the NE pressor dose ( -4 7 % and -5 1 % , p < 0.01), while the relationship between NE-induced changes in blood pressure and concomitant plasma NE concentrations was displaced to the left (p < 0.01). Supine heart rate was also lowered ( -10% and -8 % , p < 0.05). Compared to the orthostatic variations during placebo conditions, mild postural decreases in blood pressure were apparent in both the normal and hypertensive groups ( -8% and -7.5%). However, supine blood pressure was unchanged following debrisoquine treatment. Other parameters were also not consistently changed, such as total blood volume, exchangeable body sodium, urinary electrolytes, plasma epinephrine, renin, and angiotensin II (AH) levels, the pressor dose of infused All, and the relationship between All-induced changes in blood pressure and plasma AH measured before and during All infusion. These findings demonstrate that the reduction in sympathetic outflow during sympathetic neuron blockade may elicit a hyperresponsiveness of alpha-and beta-adrenergic receptors that is equal in normal subjects and patients with mild essential hypertension. (Hypertension 5: 873-880, 1983) KEY WORDS.• sympathetic nervous system • sympathetic inhibition blood pressure regulation • norepinephrine • renin • angiotensin II cardiovascular pressor responsiveness • cardiac beta-receptor response T HE arterial blood pressure is determined both by the absolute quantities of pressor factors and by cardiovascular responsiveness. In normal humans, the pressor effects of norepinephrine (NE) and angiotensin II (All) correlate inversely with their preexisting blood levels, 1 " 1 and this may contribute to blood pressure homeostasis. However, cardiovascular NE responsiveness tends to be exaggerated relative to plasma NE concentrations in normotensive offspring of hypertensive families 4 and patients with borderline 5 or established 23 -6 essential hypertension. Moreover,

Blood levels and renal effects of atrial natriuretic peptide in normal man.

“…Hematocrit was measured by the microcrit method, plasma and urinary 5"Cr activity in a -y-counter (Tri-Crab-Scintillation spectrometer, Packard Instrument Co., Downers Grove, IL), PAH by standard photometric method, sodium and potassium by flame photometer, and chloride, calcium, magnesium, phosphate, uric acid, urea, and creatinine by autoanalyzer (Greiner Societ6 Anonyme, Langenthal, Switzerland). Osmolality was measured by freezing point depression using a cryoscope with Peltier's element, plasma protein by the biuret method, and plasma renin activity, angiotensin II, and aldosterone levels by radioimmunoassay (29)(30)(31), as reported previously from our laboratory (27,32). Plasma and urinary norepinephrine, epinephrine, and dopamine were determined with high performance liquid chromatography and electrochemical detection using a modified method ofSmedes et al (33).…”

Alpha 1-adrenergic blockade and cardiovascular pressor responses in essential hypertension.

“…A 5% dextrose solution was infused over 20 minutes, and an isoproterenol sensitivity test was performed with bolus injections of 0.2, 0.4, 0.8, 1.6 pig, and, if the increase in heart rate did not reach 25 beats/ min, 3.2 and 6.4 fig of isoproterenol hydrochloride. 13 Heart rate was monitored by electrocardiography. The resting rate was calculated as the mean from 10 consecutive RR intervals, while the heart rate after isoproterenol injection was calculated from the three shortest RR intervals.…”

“…13 -l4 The dextrose solution was then replaced by a solution of /-NE bitartrate in 5% dextrose, which was infused at stepwise increasing dose rates of approximately 20, 40, 100, and 200 ng/kg/min lasting 20 minutes each. 13 During the last 10 minutes of each infusion step, blood pressure and heart rate were recorded every minute using a cuff and the automatic recorder Sphygmodigital 4000 (Asulab S. A. Neuenburg, Switzerland)." At the end of each infusion step, plasma NE and epinephrine levels were measured.…”

“…At the end of this second equilibration period, basal blood pressure, heart rate, plasma renin activity, and ANG II and aldosterone levels were determined. 13 The dextrose infusion then was replaced by a solution of ANG II (Hypertensin, Ciba-Geigy, Basle, Switzerland) in 5% dextrose, which was infused at increasing dose rates of 2, 4, 10, and 20 ng/kg/min lasting 20 minutes each. Blood pressure and heart rate were monitored as just described above, and plasma ANG II and aldosterone levels were determined at the end of each ANG II infusion step.…”

Temporary Reduction of Blood Pressure and Sympathetic Nerve Activity in Hypertensive Patients After Microvascular Decompression

“…It can be considered that the reduction of sympathetic nerve activity by surgical decompression may elicit an increased cardiovascular adrenergic responsiveness, as has been shown for pharmacological sympathetic neuron blockade. 18 Other components of the pathogenesis of essential hypertension such as genetic factors, overweight, neurohumoral function, vasopressor-receptor resetting, and stress, which may all interact together and with the sympathetic nervous system, have to be considered as reasons for the repeated increase of blood pressure.…”