Phentolamine testing for alpha adrenergic participation in hypertensive patients: Independence from renin profiles

Abstract

To evaluate alpha adrenergic participation in sustaining blood pressure levels in hypertension. phentolanine. I mglmin for 20 min. was infUsed into 30 seated hypertensive patients. An average fall in diastolic blood pressure of 13.9 ± 9.2 (SD) mm Hg was induced: 21 of the 30 patients (70%) experienced a fall of at least 10%. Systolic blood pressure fell by 7.8 ± 15.7 mm H g. a decrement less (p < 0.05) than that for diastolic pressure. Heart rate increased by 36.2 ± 19.8 bpm and plasma renin activity increased by 1.5 ± 2.6 ng Iml Ihr during infusion. These increases did not correlate with the induced blood pressure changes and. thus. presumably reflected either the alpha blocking or perhaps beta agonistic properties of phentolamine. When patients were subdivided according to their renin-sodium indices. there were no differences between the high. normal. and low renin subgroups in response to phentolamine and there was no correlation between control plasma renin activity and induced changes in systolic or diastolic blood pressure. Furthermore. in 24 patients who separately received an angiotensin-converting enzyme inhibitor. teprotide. there was no relationship between the blood pressure decrements induced by it and those induced by phentolamine. In 13 patients in whom renin levels were stimulated by a restricted sodium diet. the blood pressure response to phentolamine was the same as that when they were studied on an unrestricted sodium diet. The results suggest that alpha adrenergic factors may often participate in sustaining blood pressure in hypertensive patients. This role is independent of the renin-angiotensin system and of the state of sodium balance.Numerous reports indicate that plasma catecholamine levels are elevated in patients with essential hypertension. 6,9, 11,13,23 Moreover. Louis and associates 22 • 23 have reported a direct relationship between plasma catecholamine concentrations and diastolic blood pressures in such patients. It also has been claimed that there may be a relationship between plasma levels of catecholamines and plasma renin activity. the highest concentrations of catecholamines occurring in patients classified as having high renin forms of hypertension.8, 10, 12, 14-16

Plasma Noradrenaline Concentration and α-Adrenoceptor-Mediated Vasoconstriction in Normotensive and Hypertensive Man

“…The correlations in hypertensive, but not in normotensive, subjects between both plasma noradrenaline and the vascular e-adrenoceptorblocking effect of phentolamine and blood pressure suggest that it is more a difference in the pattern in which sympathetic activity and blood pressure inter-relate rather than a disturbance of sympathetic activity per se. Our data therefore indicate that sympathetic activity may be directly related to the level of blood pressure in patients with essential hypertension, which is in agreement with the observations of correlations between the decrease in blood pressure after either ganglionic blockade (Tarazi & Dustan, 1973) or the systemic application of phentolamine (Drayer et al, 1977) and control blood pressure in essential hypertension. In as much as correlations can be taken as evidence of cause and effect this could mean that sympathetic activity may be more important for the determination of blood pressure in hypertensive than in normotensive subjects.…”

“…It was probably of no great importance in our study, since complete sympathetic blockade by means of deep nerve blockade in normal volunteer subjects 'resulted in an average increase in forearm blood flow of approximately 100% (Barcroft, Bonnar, Edholm & Effron, 1943), a value similar to our results. There is some evidence that phentolamine may have fJadrenoceptor-stimulating properties (Zahir & Gould, 1971;Drayer et al, 1977), an effect that was allowed for by establishing {J-adrenoceptor blockade before phentolamine infusion. A different effect of acute fJ-adrenoceptor blockade in hypertensive as compared with normotensive subjects could conceivably influence the response to phentolamine.…”

“…Phentolamine is an a-adrenoceptor antagonist and the vasodilatation after its administration is highly dependent on the presence of an intact sympathetic vascular innervation (Cammarata" Langley, Dugan, Lattima, Smith, Tessman & Kaplan, 1978;Lefevre-Borg, Roach & Cavero, 1978). In addition it may have fJadrenoceptor stimulatory effects (Zahir & Gould, 1971;Drayer, Weber, Atlas & Laragh, 1977). Thus before phentolamine infusion we first established systemic ,B-adrenoceptor blockade (propranolol 0·2 mg/kg, intravenously).…”

Medicinal Chemistry and Animal Pharmacology of Indoramin

“…The compounds then available were not widely adopted for a variety of reasons, including poor absorption, lack of specificity, gastrointestinal disturbances, development of tolerance, postural hypotension, and reflex tachycardia. Yet Brownlee (1966) (Drayer et al, 1977). Given this information, and the knowledge that increased peripheral resistance is the main functional abnormality in essential hypertension (Bowman & Rand, 1980), the desirability of seeking to overcome the drawbacks of older a-blockers should be apparent.…”

The Effect of Phentolamine on Active and Inactive Renin Release in Human Renovascular Hypertension

“…, 1979;Levy et al, 1977). In patients with essential hypertension, phentolamine increases PRA (Drayer et al, 1977;Levy et al, 1977) while in patients with phaechromocytoma, long-term wadrenoreceptor blockade with phenoxybenzamine reduced PRA (Vetter et al, 1976).…”