Adrenal Medullary Blood Flow Research Articles

Regional adrenal blood flow responses to adrenocorticotropic hormone after chronic embolization of the fetal placental circulation in sheep.

To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic-pituitary-adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 microns microspheres for 8 days from about day 124 of gestation (term approximately 147 days) and sham-embolized controls. Starting before the final embolization (or sham-embolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1-24 (0.5 microgram/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 +/ 15 vs 292 +/- 25 ml/min per 100 g tissue; mean +/- S.E.; P<0.01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and sham-embolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0.05) due to decreased vascular resistance (P<0.01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments.

Cholinergic regulation of adrenal medullary blood flow

To determine the relative role of nicotinic and muscarinic mechanisms in splanchnic nerve stimulation (NS)-induced adrenal catecholamine secretion and medullary vasodilation, 12 pentobarbital-anesthetized dogs were subjected to three identical stimulations. The first NS was performed before drug administration and served as a control. The second NS was performed after administration of either the muscarinic antagonist, atropine 0.5 mg/kg (group 1), or the nicotinic antagonist, hexamethonium 20 mg/kg (group 2). The third NS was performed after administration of both drugs. NS in the absence of drug resulted in 4-fold and greater than 200-fold increases in medullary blood flow (Q, measured with radiolabeled microspheres) and catecholamine secretion (assayed by high-pressure liquid chromatography), respectively. Atropine, when administered alone (group 1), had no effect on these responses. Subsequent administration of hexamethonium to group 1 animals resulted in complete blockade of NS-induced changes in medullary Q and secretion. Hexamethonium alone (group 2) reduced the catecholamine response to NS by 95% but had no effect on the medullary Q response. Addition of atropine further attenuated the increase in catecholamine secretion induced by NS and completely blocked the medullary Q increase. These data suggest the presence of redundant mechanisms to increase medullary Q during NS. One mechanism likely involves neurally released acetylcholine-stimulating vascular muscarinic receptors, whereas the second requires either chromaffin cell degranulation or nicotinic ganglionic transmission.

Subarachnoid Blockade Alters Homeostasis by Modifying Compensatory Splanchnic Responses to Hemorrhagic Hypotension

To demonstrate that sympathetic responses transmitted by the splanchnic nerve help maintain intravascular stability, 12 mongrel dogs (35-45 kg each), anesthetized with pentobarbital, were given two separate but identical hypotensive stimuli (mean arterial blood pressure of 60 mm Hg for 15 min) by the withdrawal of appropriate amounts of blood. The first stimulus was performed in the absence of drug or surgical manipulation. The second stimulus was performed after animals were subjected to no intervention (n = 4), bilateral splanchnic nerve section (n = 4), or spinal anesthesia (n = 4). Before and 10 min after the onset of hypotension, arterial epinephrine concentration and adrenal medullary and abdominal organ blood flow were measured. In the group without intervention, the second hypotensive stimulus (like the first) elicited 3-fold increases in adrenal medullary blood flow, 40-fold increases in arterial epinephrine concentration, and a 61% reduction in abdominal organ blood flow (P greater than 0.002). The volume of blood withdrawn to produce hypotension was similar (approximately 21 ml.kg-1). Bilateral splanchnic nerve section attenuated the adrenal medullary blood flow, arterial epinephrine concentration, and abdominal organ blood flow responses to hypotension by 86, 64, and 66%, respectively (P less than 0.008), and the blood volume withdrawn was reduced by 42% (P less than 0.02). Spinal anesthesia eliminated the adrenal medullary blood flow response to hypotension, attenuated the arterial epinephrine concentration and abdominal organ blood flow responses by 78 and 57%, respectively (P less than 0.01), and decreased the blood volume extracted by 55% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of adrenal hypotension on elicited secretory activity in anesthetized dogs

The objective of this study was to determine whether three- to fourfold increases in adrenal medullary blood flow (MQ), observed during catecholamine secretion induced by splanchnic nerve stimulation (NS), are necessary for a maximal secretory response. Eight pentobarbital-anesthetized adult male mongrel dogs (25-35 kg) were subjected to two episodes of NS-induced catecholamine secretion. To limit increases in MQ, one NS (20 Hz, 8 V, 1.5 ms) was performed under control conditions, the other was after reduction of adrenal perfusion pressure (PP). PP was 124.8 +/- 6.0 at control and was reduced to 23.0 +/- 1.0 mmHg by inflation of an aortic occluder located 3 in. above the adrenals. NS under control conditions increased ipsilateral MQ (measured using radiolabeled microspheres) from 181 +/- 39 to 1,336 +/- 199 ml.min-1.100 g-1 and adrenal epinephrine secretion from 184 +/- 128 to 11,445 +/- 5,216 ng.min-1.g medulla-1. Contralateral MQ and cortical blood flow were unaffected by NS. Reduction of PP decreased MQ to 32 +/- 6 ml.min-1.100 g-1 and adrenal cortical blood flow from 251 +/- 23 to 25 +/- 6 ml.min-1.100 g-1.PP reduction had no effect on either corticosteroid secretion or unstimulated epinephrine secretion. NS at reduced PP increased ipsilateral MQ to 146 +/- 27 ml.min-1.100 g-1 and epinephrine secretion to 13,935 +/- 5,175 ng.min-1.g medulla-1. These data indicate that epinephrine secretion is not altered when MQ is limited by reduction of PP and suggest that, at normal PP, increases in MQ during catecholamine secretion are not necessary for a maximal secretory response.(ABSTRACT TRUNCATED AT 250 WORDS)

ESMOLOL HYDROCHLORIDE, SODIUM NITROPRUSSIDE, AND ISOFLURANE DIFFER IN THEIR ABILITY TO ALTER PERIPHERAL SYMPATHETIC RESPONSES

To demonstrate that esmolol, sodium nitroprusside, and isoflurane differ in their abilities to alter adrenal medullary blood flow and other peripheral sympathetic responses to hypotension, 16 mongrel dogs anesthetized with pentobarbital were allocated randomly to one of four test groups and given two hypotensive stimuli, separated by 1 h, to a mean arterial blood pressure of 60 mm Hg for 10 min. The first stimulus, induced by blood loss into a pressurized bottle system, constituted the control for each animal. The second hypotensive stimulus was created by either repeat blood loss (Group 1), esmolol infusion (Group 2), sodium nitroprusside infusion (Group 3), or isoflurane administration (Group 4). Before and 10 min into hypotension, the variables of abdominal organ blood flow, adrenal medullary blood flow, arterial norepinephrine and epinephrine concentrations were measured. In the control animals (Group 1), comparable decreases in abdominal organ blood flow and similar increases in adrenal medullary blood flow, norepinephrine, and epinephrine were elicited by the first and second hypotensive stimulus. Esmolol-induced hypotension (Group 2) abolished the increase in adrenal medullary blood flow and attenuated the increase in epinephrine by 65% (P < 0.03). The decrease in abdominal organ blood flow and the increase in norepinephrine were similar to that observed during baseline hemorrhagic hypotension. In contrast, sodium nitroprusside-induced hypotension (Group 3) abolished abdominal organ vasoconstriction whereas the increases in adrenal medullary blood flow, norepinephrine, and epinephrine were comparable to baseline hemorrhagic hypotension. In fact, abdominal organ blood flow increased 2.5-fold (P < 0.001) during hypotension with SNP. Isoflurane 2%, 1.54 minimum alveolar anesthesia concentration (Group 4), abolished the increases in adrenal medullary blood flow, norepinephrine, and epinephrine observed during baseline hemorrhagic hypotension and attenuated the decrease in abdominal organ blood flow by 70% (P < 0.001). These data demonstrate that esmolol, sodium nitroprusside, and isoflurane differ radically in their ability to alter or blunt peripheral sympathetic responses to hypotension, and suggest that isoflurane is the drug most effective in blunting multiple responses of the peripheral sympathetic system.

Adrenergic receptors of adrenal medullary vasculature.

The present study evaluates possible effects of adrenal catecholamines, released by splanchnic nerve stimulation, on adrenal medullary blood flow (MQ) and adrenal catecholamine secretion (CS). Twelve pentobarbital-anesthetized mongrel dogs were subjected to three identical splanchnic nerve stimulations (5 V, 20 Hz, for 3 min) at 30-min intervals, and MQ (radiolabeled microsphere technique) and CS (high-performance liquid chromatography) were measured before and during each nerve stimulation. Animals were assigned to one of three groups and administered either saline, pindolol (1 and 4 mg/kg), or prazosin (1 and 4 mg/kg) before the second and third nerve stimulation, respectively. In the saline control group, each nerve stimulation resulted in similar increases in MQ and CS. Pindolol attenuated nerve stimulation-induced increases in MQ and CS by 50%, but had no effect on medullary catecholamine concentration. Prazosin augmented nerve stimulation-induced MQ, CS, and medullary catecholamine concentration by 35%. These data suggest that adrenal adrenergic receptors modulate elicited CS and mediate changes in adrenal medullary vascular tone.

Neural control of adrenal medullary and cortical blood flow during hemorrhage.

Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, we compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz (n = 4 each group) for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. We conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.

Adrenal medullary and cortical blood flow during hemorrhage.

We used a radiolabeled microsphere technique to measure adrenal medullary and cortical blood flow during hemorrhagic hypotension. Twenty pentobarbital-anesthetized, ventilated, adult mongrel dogs were bled into a pressurized bottle system to reduce and maintain mean arterial blood pressure at 100, 80, 60, or 40 mmHg (n = 5/group). Blood flow was measured prior to and 2, 5, 10, 15, and 25 min posthemorrhage. Adrenal medullary blood flow increased markedly (100-400%) at all levels of hemorrhage. In contrast, decreases in cortical blood flow were observed (approximately 50%) with hemorrhage to 80, 60, and 40 mmHg. Cortical blood flow returned to control levels at 25 min, except in the 40-mmHg group. Whole adrenal gland blood flow showed early, transient decreases, consistent with the fact that the adrenal cortex comprises the bulk of the gland, but it did not precisely reflect either cortical or medullary blood flow changes. Since this method for measuring adrenal medullary and cortical blood flow was developed for the current experiment, extensive evaluation of the technique was performed (n = 31 animals). These studies included demonstration that injection of 4 X 10(6) microspheres results in sufficient numbers of microspheres in the adrenal medulla and cortex to permit estimation of blood flow (greater than or equal to 400 spheres/sample), that 15-micron spheres are almost completely entrapped in the adrenal gland (greater than 98%), that multiple injections of microspheres (n = 5) do not alter blood flow, and that streaming of microspheres does not appear to occur to any significant extent in this vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)