Studies on acute tolerance to the hypotensive effect of pindolol in conscious spontaneously hypertensive rats (SHR)

Abstract

The development and mechanism of acute tolerance to hypotension produced by pindolol in conscious SHR were examined. At a daily dose of 3 mg/kg, i.p., the hypotensive effect of pindolol (50±4 mmHg) on the first day was attenuated to 12±2 mmHg on the fourth day. The development of this acute tolerance was not reduced by combined administration with captopril or trichlormethiazide. The hypotensive effect of pindolol was not reduced by repeated administration of isoproterenol. Thus, activation of the renin-angiotensin system, fluid retention and β-adrenoceptor subsensitivity seemed to be ruled out from the mechanism of this acute tolerance to pindolol. SHR tolerant to pindolol displayed marked hypotensive effects to prazosin, clonidine, hydralazine, nifedipine and captopril, which were similar to those in saline-treated SHR. However, the depressor response to isoproterenol was markedly reduced in SHR tolerant to pindolol. The correlation between the hypotensive responses to isoproterenol (X) and pindolol (Y) in these SHR could be expressed by: Y=1.00X+0.56, γ=0.837 (P<0.001). Therefore, acute tolerance to pindolol seemed to be mainly due to “ autoblockade” by the remaining pindolol in the body.