Antihypertensive action of propranolol in man: Lack of evidence for a neural depressive effect

Abstract

The hypothesis that a neural depressive action is related to the antihypertensive effects of beta blockers has been evaluated in 14 essential hypertensive male patients through the circulatory response to noxious stimuli. The pressor reaction to mental arithmetic was primarily mediated by cardiac stimulation (beta receptors activation), that to cold by vasoconstriction (alpha receptors activation). Arithmetic and cold were tested to separate the effects of peripheral beta blackade from possible neural and other influences. After propanolol (320 mg per day for 3 wk): (1) The baseline pressure was reduced; (2) appearance, peak, and disappearance time of the circulatory reaction to either stimulus was not altered; (3) the pressor effect of arithmetic was decreased in an extent proportional to the reduced rise of cardiac output; and (4) pressure during cold reached the pretreatment levels through an augmented increase of vascular resistance. Our findings indicate that propranolol depresses only the circulatory reactions mediated through beta receptors activation and provide no evidence of effects other than beta blockade.

Responses to mental stress and physical provocations before and during long term treatment of hypertensive patients with beta‐adrenoceptor blockers or hydrochlorothiazide.

“…The mental stressor used in these studies increases cardiac output markedly and reduces the vascular resistances of the systemic circulation and skeletal muscle (Hjemdahl et al, 1984). The haemodynamic responses to CPT and ORT, on the other hand, are characterized by increased peripheral vascular resistance (Guazzi et al, 1976;Folkow et al, 1983). These differences in response patterns explain the discrepancies between increases in heart rate and venous noradrenaline levels, since the latter variable largely reflects transmitter overflow from the forearm tissues (Hjemdahl et al, 1984).…”

“…Our findings of unchanged blood pressure responsiveness to stress during 3-adrenoceptor blockade, despite attenuated heart rate responsiveness and clearly reduced blood pressure levels, are in agreement with previous findings with oral treatment with non-selective 1-adrenoceptor antagonists (Nyberg et al, 1977;Houben et al, 1983;Floras et al, 1985) or 1l-selective antagonists (Nyberg et al, 1977;Heidbreder etal., 1978;Waal-Manning & Bolli, 1980;Houben et al, 1983;Francois et al, 1984;Floras et al, 1985) for varying periods of time. Only two studies have reported decreases in blood pressure reactivity to mental stress during 3-adrenoceptor blockade (Guazzi et al, 1976;Dunn et al, 1978), but the possibility of adaptation to the stress procedure was not investigated in these studies. A study of intraarterially recorded blood pressures during the stress of driving found a reduction of blood pressure levels, but no alteration of reactivity (Millar-Craig et al, 1981), in agreement with our results.…”

The second Lilly Prize Lecture, University of Newcastle, July 1977. beta‐Adrenergic receptor blockade in hypertension, past, present and future.

“…The rise in blood pressure during the effort phase of Valsalva's manoeuvre is not inhibited by,Badrenoceptor blocking drugs (Prichard & Gillam, 1966;Prichard, Gillam & Graham, 1970), neither have more direct measurements found any evidence of inhibition of vasoconstriction (Korner, Blombery, Bobik, Tonkin & Uther, 1976). In addition, no depression of the cold pressor test was seen after 3 weeks oral propranolol in male hypertensive patients, suggesting that the innervation of the a-receptor was not impeded (Guazzi et al, 1976). Renin f-adrenergic receptor blockade in normal subjects (Winer, Chokshi, Yoon & Freedman, 1969) and hypertensives (Buhler, Laragh, Baer, Vaughan & Brunner, 1972;Michelakis & McAllister, 1972) lowers plasma renin; although the P-adrenergic system is important in the release of renin it is not the only factor (Bravo, Tarazi & Dustan, 1974).…”

“…There is some evidence that propranolol reduces the rise in blood pressure that occurs in coitus (Fox, 1970), however it does not appear to reduce the rise in pressure to painful stimuli (Nicotero, Beamer, Moutsos & Shapiro, 1968), or cold water (Guazzi, Fiorentini, Polese, Olivari & Magrini, 1976). However, it has been found that the rise in blood pressure from the stress of sorting ball bearings was reduced or abolished by 6 weeks oral propranolol or metoprolol (Lorimer, Dunn, Jones, Clark & Lawrie, 1976), and the rise in pressure in response to mental arithmetic was reduced by propranolol 320 mg a day (Guazzi et al, 1976). However, Nyberg, Graham & Stokes (1977) using lower doses of propranolol, or metoprolol, or alprenolol, found that although the peak pressures were reduced in response to mental arithmetic, the rise from base line was not.…”

Effects of cold exposure on blood pressure, heart rate and forearm blood flow in normotensives during selective and non‐selective beta‐ adrenoceptor blockade.

“…The haemodynamic effects of cold exposure during blockade with propranolol have been extensively studied (Nicotero et al, 1968;Guazzi et al, 1976;Maconochie et at., 1977;Velasco et al, 1978). As far 0306-5251/82/12086704 $01.00 as we know only one study has been published on the influence of one of the now available selective 8-adrenoceptor blockers, i.e.…”