The ROLE OF PRESYNAPTIC Α‐ADRENOCEPTORS IN THE REGULATION OF BLOOD PRESSURE IN THE CONSCIOUS RABBIT

Abstract

1 Changes in mean arterial pressure, heart rate and plasma noradrenaline after a-adrenoceptor blockade with several a-adrenoceptor antagonists have been studied in the conscious rabbit in order to investigate the possible role of presynaptic cx-adrenoceptors in cardiovascular regulation. 2 Prazosin (0.05-2 mg/kg) and phentolamine (0.5-20 mg/kg) produced dose-dependent falls in mean arterial pressure and rises in plasma noradrenaline. These changes were related to the degree of postsynaptic a-adrenoceptor blockade determined by the pressor response to intravenous phenylephrine. 3 Similar changes in mean arterial pressure and plasma noradrenaline were observed after administration of the direct vasodilators hydralazine (1-10 mg/kg) and nitroprusside (2.5 -55 g kg Imin ).4 After baroreceptor deafferentation by sinoaortic denervation the falls in mean arterial pressure were much greater and the rise in plasma noradrenaline was markedly attenuated. 5 Yohimbine (1 mg/kg) increased mean arterial pressure and plasma noradrenaline but it was not possible to exclude the possibility that central nervous effects of yohimbine underlay the increased sympathetic activity. 6 The magnitude of the baroreflex response to changes in pressure make it unlikely that the functional significance of the presynaptic a-adrenoceptor can be readily determined by measurement of plasma noradrenaline in intact animals.

α‐Adrenoceptor involvement in catecholamine‐induced hyperglycaemia in conscious fasted rabbits

“…There is no clear explanation for the failure ofprazosin to produce a complete block, since the drug behaves as a very potent antagonist of Ad-induced activation of glycogen phosphorylase in rat isolated hepatocytes (Aggerbeck et al, 1980a,b). Also prazosin at a dose of I mg kg-' should certainly block postsynaptic al-adrenoceptors in the rabbit, though this blockade would have been accompanied by a simultaneous increase in circulating NA plasma levels (Hamilton et al, 1982). This increase could in theory interfere with the response to be blocked.…”

“…Effects ofphenylephrine in the presence ofcadrenoceptor blocking drugs Bearing in mind that phenylephrine is an x-adrenoceptor agonist with affinity for al-and C2-adrenoceptors (McGrath, 1982) that 1 mg kg-' prazosin exerted a very good degree of postsynaptic x1-adrenoceptor blockade (Hamilton et al, 1982). However, 1 mg kgI prazosin, when injected s.c. 30 min before the agonist, attenuated the effect of PE on blood glucose (Figure 2a).…”

“…infusion of prazosin at 0.5 to 10 gkg-min' administered for 30 min just before PE, reduced the hyperglycaemic effect of this agonist in much the same way as did the larger dose (data not presented). These smaller doses of prazosin should not induce any appreciable increase in NA plasma levels (Hamilton et al, 1982).…”

“…Since prazosin at the dose tested in this study could certainly elevate circulating levels of plasma NA (Hamilton et al, 1982), which in turn might interfere with the response to be blocked, smaller doses of this al-selective antagonist were also examined. Again an i.v.…”

Yohimbine and prolongation of stimulation pulse duration alter similarly 3H‐transmitter efflux in heart: an alternative to the negative feedback hypothesis

“…However, a number of studies now question seriously the credibility of feedback regulation (e.g. Kalsner, 1979a,b;1982a,b;Angus & Korner, 1980;Drew, 1980;Holman & Surprenant, 1980;Robie, 1980;Blakeley, Cunnane & Peterson, 1982;Hamilton, Reid & Zamboulis, 1982).…”