The role of renal dopamine in the reduction of high blood pressure by beta 1-selective beta-blocker with intrinsic sympathomimetic activity in spontaneously hypertensive rats

Hypertens Res. 1995 Jun:18 Suppl 1:S215-9. doi: 10.1291/hypres.18.supplementi_s215.

Abstract

The present experiments were undertaken to clarify the difference of renal dopamine production from beta 1-selective beta-blocker with and without intrinsic sympathomimetic activity (ISA). Either beta-blocker with ISA, celiprolol (100 or 300 mg/kg/day; CEL-100 or CEL-300) or beta-blocker without ISA, atenolol (50 mg/kg/day; ATE-50) was administered to the SHR from 19 to 26 weeks. Degrees of lowering blood pressure in CEL-300 SHR and in ATE-50 SHR were similar, but decrease in heart rate was significantly less in CEL-300 SHR than in ATE-50 SHR. Urine output, which was significantly less in control SHR than in control WKY, was significantly greater in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. Urinary excretions of noradrenaline (u-NA) and dopamine (u-DA) were significantly higher in control SHR than in control WKY and a comparable u-DA/u-NA ratio was found in these two groups. U-DA and the ratio of u-DA/u-NA were significantly elevated in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. There was a significant positive correlation between u-DA/u-NA ratio and urine output and a significant negative correlation between the ratio of u-DA/u-NA and change of blood pressure in control SHR, CEL-100 SHR and CEL-300 SHR. These results suggest that an enhancement of renal dopamine production by ISA (beta 2 stimulation) of beta 1-selective beta-blocker may contribute, at least in part, to the antihypertensive effect of this drug.

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists*
  • Adrenergic beta-Antagonists / therapeutic use*
  • Animals
  • Atenolol / therapeutic use
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Celiprolol / therapeutic use
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Dopamine / urine
  • Heart Rate / drug effects
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / physiopathology
  • Kidney / metabolism
  • Kidney / physiopathology*
  • Male
  • Norepinephrine / urine
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sympathomimetics / therapeutic use*
  • Urodynamics / drug effects

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Sympathomimetics
  • Atenolol
  • Celiprolol
  • Dopamine
  • Norepinephrine