Effects of depleting central and peripheral adrenaline stores on blood pressure in stroke-prone spontaneously hypertensive rats.

The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). alpha-Monofluoromethyldopa, a long-lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine-N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appear to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP.

Separate areas of rat medulla oblongata with populations of serotonin- and adrenaline-containing neurons alter blood pressure after L-glutamate stimulation.

Separate populations of serotonin- and adrenaline-containing neurons exist in the ventrolateral medulla oblongata and project to the intermediolateral cell column of the spinal cord. The medullary serotonin nuclei appear to constitute a heterogeneous group with diverse effects on arterial pressure. Microinjections of sodium glutamate (which excites cell bodies but not axons of passage) made in the area of the ventrolateral serotonin cells evokes an increase in arterial pressure which is abolished by prior 5,7-dihydroxytryptamine (5,7-DHT) treatment. In contrast, glutamate microinjection in the area of the serotonin-containing cell bodies in the midline of the medulla evokes falls in arterial pressure and these responses are attenuated by pretreatment with 5,7-DHT. Glutamate microinjection made in the ventrolateral medulla in the area of the adrenaline-containing cells, evokes increases in arterial pressure which are not altered by 5,7-DHT pretreatment. After ablation of the area of the adrenaline-containing cells by electrolytic lesion, the pressor function of the ventrolateral serotonin-containing cells is still observed. These results suggest that although the serotonin-containing neurons of the ventrolateral medulla are closely aligned with the ventrolateral adrenaline area, the serotonin cell groups and the cells of the adrenaline area exert their pressor actions independently.

A radioenzymatic assay for free and conjugated normetanephrine and octopamine excretion in man.

A radioenzymatic method for the measurement of free and conjugated normetanephrine (NMN) and octopamine (OCT) is described for human urine. The assay is based on the conversion of NMN or OCT to radiolabeled metanephrine (MN) or synephrine (SYN) by phenylethanolamine-N-methyl transferase (PNMT), using tritium-labeled S-adenosyl-methionine [3H]SAM as methyl donor. Thin-layer chromatographic separation yields an assay of high specificity. The sensitivity of the assay is 5 and 2.5 pg of NMN or OCT, respectively. The normal value of free and conjugated NMN was found to be 23 +/- 13 and 102 +/- 49 ng/mg creatinine. Four patients with pheochromocytoma had highly increased levels of free and conjugated NMN. The urinary excretions of free and total octopamine were 5.7 +/- 2.8 and 34.8 +/- 16.6 ng/mg of creatinine, respectively, in normal patients.

Modification of plasma dopamine-beta-hydroxylase activity by adrenal and pineal extirpations, and time of day dependency of changes.

Plasma level of dopamine-beta-hydroxylase (DBH; EC 1.14.2.1) activity has been considered important both as a diagnostic aid and as an indicator of temporal changes in sympathetic activity. The present study sought to evaluate the possible dependency of some phases of the circadian rhythm in plasma DBH on adrenal and pineal glands. Male Holtzman (albino) rats were shamoperated, adrenalectomized (AX), pinealectomized (PX) or both adrenalectomized and pinealectomized (AXPX) at 32-35 days of age and after acclimation to controlled conditions with a fixed, 12-h, daily photoperiod (LD 12:12). Animals were killed at selected times 15 days postoperatively, and plasma DBH was measured using a sensitive radioenzymatic method. Results from two successive experiments showed that there was significant reduction in plasma DBH in the AXPX animals, but that this was evident only during the middle of the dark phase. PX and AX alone did not bring about any change in the DBH activity at any of the two times tested. These results show that combined endocrine manipulations can alter the circulatory DBH activity level and that such changes can be evaluated only within the definition of a circadian pattern.