ORTHOSTATIC HYPOTENSION OCCURS FOLLOWING ALPHA-2-ADRENOCEPTOR BLOCKADE IN CHRONIC PRAZOSIN-PRETREATED CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

1 Studies were performed to evaluate whether chronic prazosin treatment alters the alpha-2-adrenoceptor function for orthostatic control of arterial blood pressure in conscious spontaneously hypertensive rats (SHR). 2 Conscious SHR (male 300-350g) were subjected to 90-degrees head-up tilts for 60s following acute administration of prazosin (0.1 mg kg-1 i.p.) or rauwolscine (3 mg kg-1 i.v.). Orthostatic hypotension was determined by the average decrease (%) in mean arterial pressure (MAP femoral) over the 60-s tilt period. The basal MAP of conscious SHR was reduced to a similar extent by prazosin (-23% approximately -26% MAP) and rauwolscine (-16% approximately -33% MAP). However, the head-up tilt induced orthostatic hypotension in the SHR treated with prazosin (-16% MAP, n = 6), but not in the SHR treated with rauwolscine (< +2% MAP, n = 6). 3. Conscious SHR were treated for 4 days with prazosin at 2 mg kg-1 day-1 i.p. for chronic alpha-1-adrenoceptor blockade. MAP in conscious SHR after chronic prazosin treatment was 14% lower than in the untreated SHR (n = 8). Head-up tilts in these rats did not produce orthostatic hypotension when performed either prior to or after acute dosing of prazosin (0.1 mg kg-1 i.p.). Conversely, administration of rauwolscine (3 mg kg-1 i.v.) in chronic prazosin treated SHR decreased the basal MAP by 12 approximately 31% (n = 4), and subsequent tilts induced further drops of MAP by 19 approximately 23% in these rats. 4 The pressor responses and bradycardia to the alpha-1-agonist cirazoline (0.6 and 2-mu-g kg-1 i.v.), the alpha-2-agonist Abbott-53693 (1 and 3-mu-g kg-1 i.v.), and noradrenaline (0.1 and 1.0-mu-g kg-1 i.v.) were determined in conscious SHR with and without chronic prazosin pretreatment. Both the pressor and bradycardia effects of cirazoline were abolished in chronic prazosin treated SHR (n = 4) as compared to the untreated SHR (n = 4). On the other hand, the pressor effects of Abbott-53693 were similar in both groups of SHR, but the accompanying bradycardia was greater in SHR with chronic prazosin treatment than without such treatment. Furthermore, the bradycardia that accompanied the noradrenaline-induced pressor effect in SHR was similar with and without chronic prazosin treatment despite a 47 approximately 71% reduction of the pressor effect in chronic alpha-1-receptor blocked SHR. 5 The results indicate that chronic prazosin treatment in SHR alters the alpha-1- and alpha-2-adrenoceptor function so that under continued alpha-1-receptor blockade the alpha-2-receptor mechanism(s) maintain orthostatic control of blood pressure. How an enhanced reflex bradycardia observed in chronic alpha-1 blocked SHR to the alpha-2-receptor-mediated pressor effect is related to the alpha-2-adrenergic mechanism(s) for postural homeostatic control of blood pressure remains to be further investigated.