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.
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.
Haneda
T
T
First Department of Internal Medicine, Asahikawa Medical College, Japan.
Okamoto
K
K
Hiroshima
T
T
Kashiwagi
Y
Y
Miyata
S
S
Ohi
S
S
Nakamura
Y
Y
Osaki
J
J
Hirayama
T
T
Ogawa
Y
Y
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D017272:Celiprolol / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism / Q000502:physiology* / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013566:Sympathomimetics / Q000627:therapeutic use*; D014563:Urodynamics / Q000187:drug effects
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D013566:Sympathomimetics; D001262:Atenolol; D017272:Celiprolol; D004298:Dopamine; D009638:Norepinephrine