FACILITATION BY PROCATEROL, A BETA-ADRENOCEPTOR AGONIST, OF NORADRENALINE RELEASE IN THE PITHED RAT INDEPENDENTLY OF ANGIOTENSIN-II FORMATION

1 The effects of the beta(2)-adrenoceptor agonist, procaterol, on symp athetic neuroeffector transmission were studied in the pithed adrenal demedullated rat to determine if generation of angiotensin II was invo lved in its effect. Presser responses were elicited by either electric al stimulation (20 V, 2 Hz) of the entire spinal sympathetic outflow o r methoxamine (0.1 mg kg(-1), i.v.). 2 Sodium nitroprusside (3 and 5 m u g kg(-1) min(-1), i.v.) produced hypotension and the presser respons es to both sympathetic nerve stimulation and methoxamine were reduced. This indicates that decreasing blood pressure in pithed rats reduces presser responses. Procaterol (10 and 30 ng kg(-1) min(-1), i.v.) also produced hypotension but did not alter presser responses to sympathet ic nerve stimulation. Nevertheless, procaterol (10 and 30 ng kg(-1) mi n(-1), i.v.) did reduce presser responses to methoxamine. Together the se results suggest that procaterol may have enhanced sympathetic neuro transmitter release. This was confirmed in another series of experimen ts where procaterol (30 ng kg(-1) min(-1), i.v.) increased plasma nora drenaline levels during sympathetic nerve stimulation. 3 Captopril (5 mg kg(-1), i.v.) produced hypotension and as expected reduced presser responses to sympathetic nerve stimulation. When the hypotensive effec t of captopril was abolished by concomitant vasopressin infusion (1.5- 4.5 i mu kg(-1) min(-1) i.v.), presser responses to sympathetic nerve stimulation were restored to pre-captopril levels. In this situation p rocaterol (10 and 30 ng kg(-1) min(-1), i.v.) reduced basal blood pres sure and did not alter presser responses to sympathetic nerve stimulat ion whereas the presser responses were reduced by an equihypotensive i nfusion of sodium nitroprusside (3 and 5 mu g kg(-1) min(-1), i.v.). T he lack of reduction of presser responses after procaterol in the pres ence of captopril is indirect evidence that procaterol may have enhanc ed noradrenaline release independently of angiotensin II. 4 In another series of experiments, plasma noradrenaline levels elicited by sympat hetic nerve stimulation were not altered by captopril (5 mg kg(-1), i. v.). In the presence of captopril (5 mg kg(-1), i.v.), procaterol (30 ng kg(-1) min(-1), i.v.) no longer enhanced plasma noradrenaline level s during sympathetic nerve stimulation. However, since the dose of cap topril is well above that required to block angiotensin converting enz yme (ACE) the effect may be non-specific. Therefore, the selective AT( 1) receptor antagonist, losartan (10 mg kg(-1), i.v.), was also used. Losartan (10 mg kg(-1), i.v.) did not alter plasma noradrenaline level s during sympathetic nerve stimulation, and in the presence of losarta n procaterol (30 ng kg(-1) min(-1), i.v.) enhanced plasma noradrenalin e levels during sympathetic nerve stimulation. This result further sug gests that beta-adrenoceptor facilitation of noradrenaline release fro m sympathetic nerves in the pithed rat occurs by a mechanism independe nt of angiotensin II generation.