R. Boucher

Autonomic Nervous System and Benign Essential Hypertension in Man

The clinical entity of benign essential hypertension is often subdivided into labile essential hypertension and stable essential hypertension. To establish less arbitrary limits between normotension and labile and stable benign essential hypertension, 70 subjects (56 with benign essential hypertension) were classified according to (a) the usual blood pressure index for each subject and (b) the upper limit of variation of the usual blood pressure indexes of a normotensive population. Catecholamines, plasma renin activity, and urinary creatinine, sodium, and potassium were measured in recumbent subjects who had received a controlled-sodium diet. Our findings suggest that (1) benign essential hypertension represents a heterogeneous entity and a continuous spectrum of clinical and biochemical changes when it is related to the level of blood pressure, (2) adrenergic involvement is more evident in labile hypertension, (3) regardless of the urinary excretion of catecholamines in subjects with benign essential hypertension the urinary ratio of dopamine to norepinephrine always remains lower, and (4) a negative correlation exists between urinary sodium excretion and usual blood pressure indexes.

Renin-Aldosterone System in Parkinson's Disease

Low blood pressure is frequent in the akinetic form of Parkinsons disease. A low renin activity in plasma as well as a low rate of aldosterone secretion is demonstrated in these patients. Renin activity in the plasma is further decreased by treatment with L-dihy-droxyphenylalanine, thus partially accouinting for the hypotensive episodes seen with this form of therapy.

Effects of angiotensin II on steroid metabolism and hepatic blood flow in man.

SUMMARY Metabolic clearance rates (MCR) of aldosterone, cortisol, 11-deoxycorticosterone (DOC), corticosterone, and progesterone were simultaneously measured by constant infusion in eight control subjects before and during angiotensin II infusion in subpressor (3 ng/min per kg) and pressor (22 ng/min per kg) doses. Plasma levels of aldosterone and cortisol, the heat-labile protein-bound fraction of aldosterone, and hepatic blood flow (HBF) (as estimated by the fractional clearance of indocyanine green) were determined concomitantly. Angiotensin II in a subpressor dose produced a significant decrease of the MCR of aldosterone (by 23%), cortisol (by 16%), DOC (by 26%), corticosterone (by 14%) and progesterone (by 33%). The pressor dose further decreased the respective MCR by 37%, 21%, 40%, 28%, and 42% of the baseline value. Plasma aldosterone levels rose by 317% with subpressor and by 434% with pressor doses. HBF decreased by 18% with subpressor and by 33% with pressor doses of angiotensin II. Furthermore, there were significant negative correlations between the MCR of each steroid and the respective values of the fractional clearance of indocyanine green. We conclude that angiotensin II, by its vasoconstrictive action on the splanchnic vascular bed, decreases the MCR of aldosterone, cortisol, DOC, corticosterone, and progesterone. This decrease has to be taken into account when considering the stimulatory effect of angiotensin II on various plasma steroid concentrations.

Tonin, angiotensin II system. A review.

SUMMARY A review on a new enzyme capable of forming angiotensin II in tissues without passing along the classic angiotensin I pathway, is reported. This enzyme is different from renin, pseudorenin, and angiotensin I-converting enzyme.

Substrate specificity of tonin from rat submaxillary gland.

The substrate specificity of tonin from rat submaxillary gland was examined with a series of synthetic peptides encompassing the C-terminus of the decapeptide substrate angioten-sin I. In contrast to angioteosin I-converting enzyme from plasma or lung, only angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I are substrates of tonin with Km values of 34.5 &mgr;M, 39.3 &mgr;M, and 54.4&mgr;M, respectively, while the shorter C-terminal peptides are not hydrolyzed. Thus, the N-terminal sequence extending from position 1 to 3 is the enzymatic binding site for tonin. Turnover numbers of 33.4 sec-1, 42.8 sec-1, and 6.5 sec-1 are observed for the hydrolysis of angiotensin I, (des-Asp1)- angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I, respectively. The relative percentage rates of hydrolysis (proportional to V/Km)at low substrate concentrations ([S] << Km ) are almost identical for (des-Asp1)-angiotensin I, angiotensin I, and the tetradecapeptide substrate, indicating that these three peptides are equally good substrates at low physiological concentrations. The observed high specificity of the enzyme lends support to the possible important role of tonin for local conversion in tissue. The conversion of (des-Asp1)-angiotensin I to (des-Asp11)-angiotensin II (angiotensin III) is of particular interest in relation to the recently suggested, potential role of the latter peptide in aldosterone release.

Autonomic Nervous System and Benign Essential Hypertension in Man II. Circulatory and Hormonal Responses to Upright Posture

The effect of upright posture as a physiological stimulus of the adrenergic nervous system was studied in 56 subjects with benign essential hypertension. The subjects received a controlled-sodium diet. Blood pressure, heart rate, catecholamines, plasma renin activity, and urinary creatinine, sodium, and potassium excretion were measured in the recumbent and upright positions. We found an alteration in the blood pressure response in subjects with benign essential hypertension; the postural increase in the mean blood pressure in normotensive subjects (3.18 ± 1.35 mm Hg) progressively disappeared and was replaced by a postural decrease in subjects with more severe stable hypertension (−6.71 ± 2.42 mm Hg). The hypertensive subjects also lacked the usual increase in urinary excretion of norepinephrine. A significant increase in plasma renin activity associated with a significant decrease in plasma norepinephrine occurred in subjects with labile hypertension with postural tachycardia. Finally, we found a highly significant correlation between the excretion of sodium and potassium in the recumbent position and the retention of both ions in the upright position.

Labile (Borderline) Hypertension—New Aspects of a Common Disorder:

Labile hypertension in patients under 50 years of age (the non-atherosclerotic form) was found to be characterized by higher urinary excretion of catecholamines and particularly of homovanillic acid; when further analyzed it was shown to be a heterogeneous entity with two types of patients clinically and biochemically distinguishable from each other, from control subjects and from patients with stable hypertension. Reactivity to assuming an upright posture distinguishes one type of labile hypertension having a normal postural pulse rate response from another having an excessive postural increase in pulse rate. The first group also showed normal responses of plasma norepinephrine concentration and of urinary cyclic AMP to posture. The group with excessive pulse rate response, in contrast, showed a decrease in plasma norepinephrine and an excessive increase of urinary cyclic AMP excretion in response to upright posture. The results suggest that not only circulating catecholamines but also the reactivity of their target tissues (as probably reflected by cyclic AMP measurements) are important in bringing about signs of adrenergic excess. The hypothesis that cyclic AMP changes reflect beta-adrenergic receptor reactivity is strongly favoured by data indicating qualitative differences in cyclic AMP responses to beta-adrenergic stimulation or inhibition between control subjects and those labile hypertensive patients with clinical signs of excessive sympathetic reactivity. The study stresses the need for more precise definition of labile hypertension, for dynamic clinical and biochemical correlative studies, and for consideration not only of the circulating hormones but also of the second messengers (such as cyclic AMP and cyclic GMP) which reflect the cellular action of hormones. Blood pressure is a very labile parameter in health and disease. In one sense, therefore, hypertension can be considered labile in every hypertensive patient. Usually, however, labile (or borderline) hypertension is regarded as characterized by a blood pressure over 140/90 mmHg, falling below these values with physical and emotional rest. This clinical entity, which affects some 20% (variously estimated between 16 and 30%) of the adult population, gives rise to uncertainties in both definition and prognosis. In some patients labile hypertension represents the precursor of a fixed hypertensive state, whereas in many others it remains labile throughout life, never progressing to the stable phase nor becoming associated with hypertensive cardiovascular disease.(ABSTRACT TRUNCATED AT 400 WORDS)