Inhibition of adrenaline-forming enzyme in the brain prevents one-kidney, one-clip hypertension and deoxycorticosterone acetate-salt hypertension in the rabbit.
1. Phenylethanolamine N-methyltransferase (PNMT) converts noradrenaline into adrenaline and brain PNMT is elevated in spontaneously hypertensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In view of the evidence for the involvement of central adrenergic neurons in renal hypertension, we measured the blood pressure response in one-clip, one-kidney Goldblatt hypertensive and DOCA-salt hypertensive rabbits to the PNMT inhibitor SK&F 64139, injected into the lateral cerebral ventricles. 2. Intracerebroventricular injection of SK&F 64139 (10 micrograms/kg) significantly attenuated the mean arterial blood pressure rise in one-clip, one-kidney and DOCA-salt rabbits, at 4 and 8 weeks. 3. These findings support the idea the hypertension in this animal model required an intact adrenaline biosynthetic process, and that central catecholaminergic neurons may be involved in the pathogenesis of low-renin dependent forms of hypertension.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000201:enzymology*; D003900:Desoxycorticosterone / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D011817:Rabbits; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D003900:Desoxycorticosterone; C012153:7,8-dichloro-1,2,3,4-tetrahydroisoquinoline; D010625:Phenylethanolamine N-Methyltransferase