Resistance of noradrenaline in blood vessels to depletion by 6‐hydroxydopamine or immunosympathectomy

Abstract

Summary1. The degree of the decrease in the noradrenaline concentrations caused by 6-hydroxydopamine or immunosympathectomy was different in different areas of the cardiovascular system. 2. In rats or guinea-pigs 6-hydroxydopamine depleted the noradrenaline content of the heart by 90%, of the mesenteric vein by 80% and of the mesenteric artery and aorta by 30-60%. Immunosympathectomy elicited a 70% reduction in the cardiac noradrenaline but only a 50% reduction in the noradrenaline of the blood vessels of the rat. 3. The tyrosine hydroxylase activity of the heart, blood vessels, or adrenal glands was not significantly altered 2 weeks after 6-hydroxydopamine. Nor was the monoamine oxidase activity in heart or blood vessels changed. 4. The inconsistent ability of both 6-hydroxydopamine and immunosympathectomy to abolish experimental hypertension may be due to the partial persistence of noradrenaline and functional sympathetic nervous system activity in the blood vessels.

Monoamine oxidase in rat arteries: evidence for different forms and selective localization

“…The animals were killed on day 9 (Thoenen & Tranzer, 1968). Difficulties in producing chemical sympathectomy of vascular tissues have been reported (Goldman & Jacobowitz, 1971;Berkowitz, Spector & Tarver, 1972). The latter authors determined MAO activity in mesenteric artery on day 15 of the injection schedule (Thoenen & Tranzer, 1968) and did not find a significant reduction following 6-OHDA.…”

The effects of an anti‐atherosclerotic drug, pyridinolcarbamate, on heart, vascular and brain biogenic amines

“…Rats were killed by cervical dislocation and tissues rapidly dissected out, frozen on dry ice and stored frozen until analysed. Vascular tissues were pooled and fluorometrically assayed for noradrenaline as previously described (Berkowitz, Tarver & Spector, 1971 ;Berkowitz, Spector & Tarver, 1972). Heart and brain were assayed individually for noradrenaline (Anton & Sayre, 1962) or 5 hydroxytryptamine (Snyder, Axelrod & Zweig, 1965 (Shimamoto, Takeuchi & Ishiaka, 1962;Shimamoto & Sunaga, 1962 (Shimamoto, Malzawa, Yamazaki, Atsumi, Fijita, Ishioka & Sunaga, 1966;Kipshidze, 1972;Lund, 1972).…”

Chemical sympathectomy alters the development of hypertension in miniature swine.

“…14 ' 17 Although we cannot exclude these possibilities because we did not directly assess the vascular nerves, they are unlikely explanations for these results considering the chronic treatment with 6-OHDA (4-5 months), depletion of norepinephrine in all tissues that were assayed, and the other strong indications of a peripheral sympathectomy that were discussed above. Because hypertension is multifacto-rial in nature and mineralocorticoids are known to influence renal function, vascular reactivity, and vasopressin secretion, 24 it seems likely that there is an interplay between both neural and nonneural components during the development of DOCA hypertension.…”

“…Blood vessels seem to be particularly resistant to norepinephrine depletion by 6-OHDA, but it has been suggested that these differences could be overcome if a sufficient amount of 6-OHDA were to be used. 17 Factors affecting the degree of sympathectomy attained with 6-OHDA include 1) a critical dose of 6-OHDA for destruction of nerve terminals, 2) the amount of blood flow to the organ, 3) the density of adrenergic innervation, and 4) the degree of maturation of nerve fibers at the time of treatment. 6 Although we did not measure any vascular norepinephrine content in this study, the degree of norepinephrine depletion found in the tissues that were sampled (more than 93%) was highly indicative of an extensive sympathectomy due to chronic treatment of the animals with 6-OHDA.…”