A defective beta-hydroxylation of dopamine may precede the full development of hypertension in spontaneously hypertensive rats.
A possible mechanism of the previously observed increased adrenal dopamine release and tissue content in spontaneously hypertensive rats (SHR) was explored. The following changes in dopamine beta-hydroxylase activity and catecholamines were noted. At age four weeks (normotensive) or 12 weeks (hypertensive), SHR had lower dopamine beta-hydroxylase activity in the adrenals, heart ventricle and spleen than Wistar Kyoto rats. Tissue dopamine beta-hydroxylase activity in Wistar Kyoto rats was increased with age in the atria but decreased in the ventricles and did not change in the spleen. SHR also had reduced right heart atrial dopamine beta-hydroxylase activity in the hypertensive stage and an overall increase in atrial dopamine content even in the prehypertensive state compared to Wistar Kyoto rats. The increase in noradrenaline content seen with age in the right atrium and spleen in Wistar Kyoto rats was not found in SHR, possibly because of concomitantly decreased dopamine beta-hydroxylase activity. An augmented dopamine:noradrenaline ratio in the spleen of hypertensive SHR may also have been related to an abnormality of the synthesis of noradrenaline from dopamine not necessarily reflected by tissue dopamine beta-hydroxylase determination. A defect of beta-hydroxylation, partly attributable to deficient dopamine beta-hydroxylase activity, may thus precede hypertension and contribute to the hyperdopaminergic state found in SHR.
Kuchel
O
O
Laboratory of the Autonomic Nervous System, Clinical Research Institute of Montreal, Quebec.
Racz
K
K
Debinski
W
W
Buu
N T
NT
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D011921:Rats, Inbred WKY; D013154:Spleen / Q000378:metabolism
D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine