[Dopamine and hypertension].
Dopamine has been well recognized to be a precursor of norepinephrine, exhibiting cardiovascular effects through alpha-adrenoceptor stimulation by norepinephrine production and release in sympathetic nerve endings. It also has the specific and unique effects of natriuresis and vasodilation. Since dopamine is one of the important endogenous hypotensive and natriuretic substances, it is speculated that impaired dopamine generation and/or the disturbance of the effects of dopamine could cause hypertension with suppression of plasma renin activity and/or salt-sensitivity. A non-specific enzyme of aromatic L-amine acid decarboxylase (AAAD) converting from 3,4-dihydroxyphenylalanine (DOPA) to dopamine is widely distributed in the peripheral tissue, e.g. the sympatho-adrenomedullary system, the small intestine, the lung, the liver, the kidney, etc. Since tyrosine hydroxylase is a rate-limiting enzyme of catecholamine biosynthesis, DOPA generation in the neuronal tissues is accelerated with the sympathetic nerve activation by stress such as emotional and environmental changes, resulting in an increase of DOPA delivery to the non-neuronal tissues containing non-neuronal AAAD. More than five receptors for dopamine are cloned in the brain, and it is suggested that more than three different types of dopamine receptors are in the peripheral tissues. In spontaneously hypertensive rats, the post-receptor defect of renal dopamine D1-receptor has been proposed where peripheral dopamine generation compensatorily increased. In Dahl salt-sensitive rats, another model of genetic hypertension, the blunted response of urinary dopamine to sodium loading has been demonstrated. It is controversial whether abnormalities of the neuronal and/or non-neuronal (particularly renal) dopamine system play a contributory role on the pathogenesis of essential hypertension. However, it is plausible that the impairment of dopamine generation and/or the defective responses of a dopamine receptor might induce sodium retention and hypertension.
Sigetomi
S
S
Department of Internal Medicine III, Fukushima Medical College.
Fukuchi
S
S
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000145:classification / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002395:Catecholamines; D011954:Receptors, Dopamine; D004295:Dihydroxyphenylalanine; D012964:Sodium; D004296:Dopa Decarboxylase; D004298:Dopamine