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Abstract-Effects of clonidine on blood pressure, heart rate and rectal temperature in conscious rats were examined. Clonidine (0.1-1 mg/kg s.c.) caused a prevailing pressor response and dose-dependently a fall in heart rate and body temperature.The pressor response to clonidine (0.3 mg/kg s.c.) was completely reduced by phentolamine (10 mg/kg s.c.), chlorpromazine (10 mg/kg s.c.) but not by hexamethonium (30 mg/kg i.p.), guanethidine (30 mg/kg s.c.) or reserpine (5 mg/kg s.c. 18 hr+ 1 mg/kg i.p. 4 hr prior to clonidine). Conversely, a remarkable potentiation of the pressor response to clonidine was observed after treatment with reserpine. The bradycardia with clonidine (0.3 mg/kg s.c.) was significantly reduced by phentolamine, chlorpromazine or atropine (5 mg/kg s.c.) but was potentiated by reserpine. The hypothermia with clonidine (0.3 mg/kg s.c.) was not influenced by phentolamine or atropine but was significantly potentiated by chlorpromazine.From the above results it is suggested that the pre vailing pressor response to clonidine in conscious rats is due to a stimulation of peri pheral a-adrenoceptors, the bradycardia with clonidine is exerted through the sympa thetic pathway and the baroceptor-vagal reflex, and that the hypothermia with clonidine is mainly due to the central mechanism.

Abstract-The hypotensive mechanisms of pindolol in anesthetized and conscious rats were investigated.Pindolol caused a fall in blood pressure in anesthetized, conscious and spinal rats, though in conscious rats a higher dose of the drug was required to produce such a response.This hypotension with pindolol in anesthetized and conscious rats was markedly inhibited by pretreatment with the drug itself or other i3-adrenoceptor blocking drugs. A similar phenomenon also occurred when isoproterenol was injected intravenously in anesthetized and conscious rats. The relationship between the hypo tensive actions of four i3-adrenoceptor blocking drugs in anesthetized rats and their intrinsic F3-sympathomimetic actions in isolated catecholamine-depleted tracheal preparations was determined.Order of hypotensive potencies was the same as that of their intrinsic 13-sympathomimetic action, namely, pindolol>carteolol>bufetolol=_ propranolol (p<0.05).These results suggest that the hypotension with pindolol is mediated through a decrease in the peripheral vascular resistance due to an intrinsic ;3-sympathomimetic action of the drug.Since Prichard and Gillam (1) reported that propranolol was most effective in the clinical management of hypertensive patients, the attention of many investigators has been focused on the hypotensive mechanisms of (3-adrenoceptor blocking drugs including pro pranolol. Actually, other a-blockers have been prescribed for hypertensive patients, even though the exact hypotensive mechanisms have not been elucidated. With propranolol, however, the following hypotensive mechanisms have been suggested; 1) suppression of the renin-angiotensin system (2), 2) reduction in cardiac output (3, 4), 3) the centrally mediated hypotensive effect (5, 6), 4) the resetting of the baroceptors at a low level (1, 7, 8), etc.. Pindolol is a safe and potent hypotensive drug which has been recently introduced for clinical use in the management of hypertensive patients (9-12). The drug is a strong, potent and useful /3-blocker in cases of angina pectoris, and the myocardial depressant effect is much weaker than that of propranolol (13).The present study was undertaken to clarify the hypotensive mechanism of pindolol in both anesthetized and conscious rats. MATERIALS AND METHODSMeasurement of blood pressure and heart rate in anesthetized rats Male Wistar rats weighing 250-350 g were anesthetized with a-chloralose (80 mg/kg i.v.)-urethane (500 mg/kg i.v.). Arterial blood pressure was recorded from the right common carotid artery via a pressure transducer (Nihon Kohden, MPU-0.5) on a polygraph (San-ei

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