Effects of 5-[2-[(3-tert-butylamino-2-hydroxypropylthio)-4-thiazolyl]-2- thiophenecarboxamide hydrochloride (arotinolol, S-596) on hemodynamic and adrenergically induced renin release and renal vasoconstriction were investigated in pentobarbital anesthetized dogs. Arotinolol (1 mg/kg i.v.) decreased systemic blood pressure (SBP), heart rate (HR) and renin secretion rate without change in renal blood flow. Degree of hypotension induced by arotinolol and basal plasma renin activity prior to the injection of the drug showed significant correlation. Arotinolol (20 μg/min) produced significant suppression of renal nerve stimulation (RNS)-induced renin release and attenuated an increase in renal vascular resistance during RNS at 3 Hz. The same extent of inhibition in the renin secretion response to RNS was also obtained during the infusion of dl-propranolol (100 μg/min). The renal vasoconstriction induced by RNS and norepinephrine (NE) was inhibited dose-dependently during the infusion of arotinolol (10, 30 and 100 μg/min), phentolamine (3, 10 and 30 μg/min) or prazosin (1, 3 and 10 μg/min). Arotinolol and prazosin exerted a greater inhibitory effect on RNS- than NE-induced vasoconstriction and the opposite was true of phentolamine. Arotinolol dose-dependently decreased SBP and HR in a dose range of 0.01 to 3.0 mg/kg. The greater reduction in HR was observed with arotinolol at a lower dose range (0.01 to 0.1 mg/kg) than with propranolol. Arotinolol produced larger reduction of SBP, and less increase in carotid, vertebral, renal and external iliac vascular resistance than propranolol. These results suggest that arotinolol possesses α- and β-adrenoceptor blocking properties, which effectively contribute to the suppression of the adrenergically induced renin release and renal vasoconstriction, and to the hypotensive effect.
|Number of pages||7|
|Publication status||Published - 1988 Jan 1|
ASJC Scopus subject areas
- Drug Discovery