Catecholamine Metabolism in Hypertensive Rats

Abstract

The possible role of catecholamines in two forms of experimental hypertension in rats was investigated further. Inbred, spontaneously hypertensive (SH) Wistar rats had unchanged endogenous levels of norepinephrine (NE) in the three tissues studied, and a significantly (P<0.05) decreased rate of NE synthesis ( 14 C-tyrosine technique) in heart and brainstem but not in gut, in comparison to normotensive Wistar rats. Also, the levels of free fatty acids (FFA) and major urinary catecholamine metabolites in plasma revealed no evidence of increased catecholamine turnover or release. Sprague-Davvley rats rendered hypertensive by treatment with desoxycorticosterone acetate and 1% salt had decreased cardiac NE concentration and increased cardiac NE turnover (•''H-NE technique) and cardiomegaly, confirming the work of others. However, urinary normetanephrine and plasma FFA did not differ from those in normal rats. These and other results fail to support but do not completely exclude a primary role for catecholamines in either type of hypertension. MethodsExperiments were carried out on male SH rats and normotensive rats weighing 140 to 200 g and aged 11 to 14 weeks (8). Each hypertensive rat was carefully matched for age and weight with a normotensive control rat. Systolic blood pressure was measured weekly and on the day before each experiment in the unanesthetized state using a tail plethysmographic technique (9). The question of a suitable control for a genetic strain of rats is of fundamental importance (8). We use normotensive Wistar rats of the same strain, bred brother to sister and housed in the same animal house under the same conditions as the hypertensive rats. Both groups of rats are then treated identically, have similar growth rates, and accept skin grafts.In studies on the synthesis of NE from radioactive tyrosine, rats were given 0.5 ml 0.9% NaCl solution containing 20 fie of L-tyrosine-14 C (u.l., New England Nuclear Corporation, 370 mc/mmole) into a tail vein and were killed by decapitation at various times after injection. Blood samples were collected in heparin and centrifuged, and aliquots of plasma were analyzed for endogenous and labeled tyrosine. The heart, brainstem, and proximal ileum were removed rapidly, cooled on dry ice, homogenized in cold 0.4N perchloric acid, centrifuged, and analyzed for 14 C-labeled and endogenous NE.

Neurogenic and Humoral Factors Controlling Vascular Resistance in the Spontaneously Hypertensive Rat

“…The lesser neurogenic component, measured in response to sympathectomy, is different from that seen by Nosaka et al (5), but the reasons for the difference are not clear. The present results however are in agreement with the generally lower rate of norepinephrine turnover which has been reported in several tissues with sympathetic innervation (9)(10)(11)(12)(13) in the spontaneously hypertensive rat.…”

“…There is no standardized control animal for studies on spontaneously hypertensive rats; this lack could contribute to the differences between the present results and previously published reports. Nevertheless, when the results of these studies are placed into context along with the several reports that peripheral turnover of norepinephrine is depressed in spontaneously hypertensive rats (9,10), it seems that the search for the mechanism of spontaneous hypertension probably should not focus on the sympathetic nervous system once the hypertensive state has been established. If sympathetic innervation of blood vessels plays any role in promoting high arterial blood pressure in the spontaneously hypertensive rat, such a role perhaps should be sought in the rapidly accelerating early phase of hypertension.…”

“…Some investigators (5-7) have suggested that the hypertensive state is maintained by an increase in neurogenic vasoconstrictor influences which should theoretically be associated with 764 an increase in the turnover of catecholamines (8). However, a growing body of reports indicates a decrease in catecholamine turnover in peripheral tissues from spontaneously hypertensive rats (9)(10)(11)(12)(13). Other investigators (5,14,15) have suggested that the hypertension derives from increased reactivity to normal vasoconstrictor influences.…”

Catecholamines in kidneys of normotensive and genetically hypertensive rats. Effects of salt load.

“…24 Although under some circumstances changes in neuronal activity may alter turnover of a neurotransmitter without affecting its storage, 25 chronic alteration in sympathetic drive has been shown to affect both turnover and storage of NE; reduced activity lowers, and increased activity raises, neuronal NE content. 26 …”

Involvement of uptake1 and uptake2 in terminating the cardiovascular activity of noradrenaline in normotensive and genetically hypertensive rats.

“…It seems that there may be chronic adrenergic overactivity during the development of hypertension, as plasma levels of catecholamines and dopamine /1-hydroxylase are raised (Grobecker, Roizen, Weise, Saavedra & Kopin, 1975; Roizen, Weise, Grobecker & Kopin, 1975; Nagatsu, Ikuta, Numata, Kato, Sano, Nagatsu, Umezawa, Matsuzaki & Takeuchi, 1976; Nakamura, Suzuki & Nakamura, 1976), there is increased adrenergic drive to the heart (Pfeffer & Frohlich, 1973) and C. BELL AND R. KUSHINSKY turnover rates for cardiac noradrenaline are normal or elevated in the face of elevated blood pressure (Phelan, 1970;Louis, Krauss, Kopin & Sjoerdsma, 1970;Yamori, 1976). In addition, the vascular beds of these animals have been reported to be abnormally responsive to applied noradrenaline (McGregor & Smirk, 1968;Lais & Brody, 1975).…”