Involvement of dopamine in development of hypertension in spontaneously hypertensive rat: effect of carbidopa, inhibitor of peripheral dopa decarboxylase.
The demonstration of acceleration of hypertension was investigated in spontaneously hypertensive rats (SHR) treated with carbidopa, inhibitor of peripheral dopa decarboxylase. Oral administration of carbidopa to young SHR for 4 weeks accelerated significantly (P less than 0.05) development of hypertension as compared to SHR treated with vehicle. Urinary excretion of dopamine (DA) (P less than 0.01) and renal content of DA (P less than 0.02) were significantly decreased by carbidopa treatment. Urinary excretion of sodium (P less than 0.05) was significantly decreased and renal content of norepinephrine (NE) (P less than 0.01) was significantly increased by carbidopa. Urinary excretion of NE and epinephrine (E) did not change during the experimental period. Negative correlation between systolic blood pressure and urinary excretion of sodium (P less than 0.05) or dopamine (P less than 0.01) and positive correlation between systolic blood pressure and renal content of NE (P less than 0.05) were significantly observed in both groups of SHR treated with carbidopa and with vehicle for 4 weeks. These results suggest that decreased DA biosynthesis in peripheral tissues accelerates development of hypertension mediated by decrease of natriuresis and enhanced release of NE in the kidneys of SHR. DA plays an important role in regulation of blood pressure, and reduced dopaminergic mechanisms enhance blood pressure in SHR.
Yoshimura
M
M
Department of Medicine II, Kyoto Prefectural University of Medicine, Japan.
Kambara
S
S
Takahashi
H
H
Okabayashi
H
H
Ijichi
H
H
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000652:urine
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D012964:Sodium; D002230:Carbidopa; D004298:Dopamine; D009638:Norepinephrine