Recent aspect of the role of peripheral dopamine and its receptors in the pathogenesis of hypertension.
Dopamine is an essential and indispensable catecholamine, which acts not only as a neurotransmitter in dopaminergic and noradrenergic sympathetic neurons but also as an autocrine/paracrine substance in non-neuronal tissues. The regulatory mechanism of dopamine synthesis in neuronal tissues seems to be different from that in non-neuronal tissues. Among receptors specifically bound to dopamine, five different receptors have already been cloned. Dopamine exhibits vasodilative and natriuretic effects by stimulating specific dopamine receptors located in renal tubular cells, blood vessels, etc. Physiological effects of dopamine appear to be protective against hypertension and sodium retention. Spontaneously hypertensive rats (SHR) are known to have an enhanced dopamine generation associated with the increased sympathetic nervous activity. A defect of renal D1-receptor-mediated coupling to adenylate cyclase has also been demonstrated in SHR. On the other hand, it has been reported that Dahl salt sensitive rats exhibit defective dopamine synthesis during high salt intake, which may be a definitive abnormality in this strain. The pathophysiological role of peripheral dopamine is essential hypertensive patients is still controversial. Considering the previous studies, it seems to be the case that essential hypertensive patients with increased sympathoadrenergic activity show enhanced dopaminergic discharge where dopamine may negatively modulate high blood pressure, and that stable essential hypertensive patients with salt-sensitivity and/or suppressed renin activity show insufficient dopamine synthesis in the kidney.
Shigetomi
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S
Department of Internal Medicine III, Fukushima Medical College, Japan.
Fukuchi
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S
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011954:Receptors, Dopamine / Q000502:physiology*
D011954:Receptors, Dopamine; D004298:Dopamine