Effect of Decreased Dopamine Synthesis on the Development of Hypertension Induced by Salt Loading in Spontaneously Hypertensive Rats

Abstract

To clarify role of dopamine in the development of hypertension, the effect of a dopamine synthesis inhibitor on blood pressure and urinary output of catecholamines was investigated in spontaneously hypertensive rats (SHR) fed with high sodium diet. Rats were orally given carbidopa, an inhibitor of peripheral DOPA decarboxylase, or the vehicle for 4 weeks. Carbidopa administration accelerated significantly the development of hypertension as compared to the control SHRs with the vehicle. Carbidopa administration resulted in a significant decrease of urinary excreted sodium, urinary dopamine and renal content of dopamine. Conversely, carbidopa administration resulted in a significant increase of urinary excreted norepinephrine, urinary epinephrine and renal content of norepinephrine as compared with control SHRs. These results suggest that decreased dopamine synthesis in kidneys and probably other peripheral tissue accelerates the development of hypertension, mediated by a decrease of natriuresis and an enhancement of sympatho-adrenomedullary activity. Dopamine plays an important role in its protective action against the development of hypertension enhanced by salt loading, and decreased dopaminergic mechanisms accelerated hypertension in SHR.