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Biomedical subjects

R J Grekin

Publications and source records attributed to R J Grekin.

At least 55 records · Page 3Linked to original sources
PubMed1985

Central effects of angiotensin II and dopamine in sodium-depleted sheep.

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

Aldosterone↗
PubMed1985

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.

5-Hydroxytryptophan↗
PubMed1985

Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake.

Adult↗
PubMed1985

Alpha-melanocyte-stimulating hormone stimulation of aldosterone secretion in hypophysectomized rats.

Intact and hypophysectomized male rats on low and high sodium diets were treated with sc infused ACTH and alpha MSH, and the levels of aldosterone and corticosterone were determined in truncal blood. Plasma aldosterone levels were lower in hypophysectomized animals on the low sodium diet than in intact animals on the low sodium diet. Alpha MSH (8 micrograms/day) restored plasma levels of aldosterone to normal in hypophysectomized rats on the low sodium diet. ACTH (6 micrograms/day) did not cause significant changes in plasma levels of aldosterone in hypophysectomized animals. ACTH restored plasma corticosterone to normal in hypophysectomized rats, whereas alpha MSH had no effect on corticosterone. Alpha MSH did not increase plasma aldosterone levels in intact rats. These data suggest that alpha MSH may be important in the regulation of aldosterone secretion in the rat and that zona glomerulosa responsiveness to alpha MSH in vivo is increased by hypophysectomy. The mechanisms of alpha MSH action on glomerulosa cells are different from those of ACTH.

Adrenocorticotropic Hormone↗
PubMed1985

Peripheral serotonin2 receptor blockade does not inhibit 5-hydroxytryptophan-induced aldosterone stimulation.

To assess the effects of serotonin receptor blockade on 5-hydroxytryptophan (5HTP)-induced aldosterone secretion, we studied six normal men using the serotonin antagonists ketanserin and methysergide. The subjects were studied on three separate occasions, and pretreatment with dexamethasone was given before each study. On two occasions, the pretreatment period also included administration of a serotonin antagonist, either ketanserin (120 mg/day) or methysergide (6 mg/day). On the day of study, the subjects were given a single oral 200-mg dose of 5HTP. Plasma levels of aldosterone increased significantly after 5HTP treatment compared to basal levels during each stage of the study. No significant difference in response in the three studies was found. We conclude that peripheral blockade of serotonin2 receptors does not abolish 5HTP-induced aldosterone stimulation, and that this stimulation is most likely mediated by central pathways.

5-Hydroxytryptophan↗
PubMed1984

Scintigraphic localization of adrenal lesions in primary aldosteronism.

Dexamethasone suppression adrenal cortical scintiscanning was performed in 87 patients with primary aldosteronism. Fifty patients had adrenal cortical adenomas and 37 had bilateral adrenal hyperplasia. The diagnosis of adrenal cortical adenoma was confirmed by surgery in 49 of 50, and bilateral adrenal hyperplasia was confirmed by adrenal vein aldosterone sampling in 33 and at operation in four. Dexamethasone suppression adrenal scintigraphy correctly identified the lesion(s) in 82 of the 87 patients. There were three false-negative and two false-positive adrenal cortical scintiscanning results. Computed tomography was performed in 33 patients and correctly identified 14 of 23 patients with adrenal cortical adenomas and two of 10 patients with bilateral adrenal hyperplasia and bilateral enlarged adrenals, whereas the remaining eight were considered to have normal findings. These data indicate that, when properly performed, adrenal cortical scintigraphy is an accurate and efficacious modality for the localization of adrenal cortical adenomas and in the differentiation of adrenal cortical adenoma from bilateral adrenal hyperplasia in primary aldosteronism.

Adenoma↗
PubMed1984

Clinical syndromes associated with disorders of renal tubular chloride transport: excess and deficiency of a circulating factor?

Two contrasting patients are described, one with pseudo-Bartter's syndrome induced by frusemide abuse and the other a case of hyporeninaemic hypoaldosteronism. The clinical and biochemical features of these two conditions are the opposite of each other and, in the first patient, the effects of frusemide were antagonised by treatment with indomethacin while in the second frusemide itself corrected the syndrome. The decreased pressor sensitivity to infused angiotensin II seen in the patient with pseudo-Bartter's syndrome was corrected with indomethacin and the enhanced pressor sensitivity seen in hyporeninaemic hypoaldosteronism was reversed with frusemide. Frusemide, an agent which blocks chloride transport at the ascending limb of Henle's loop, was respectively thus the cause and the cure of these conditions. On the basis of this the suggestion is made that Bartter's syndrome and hyporeninaemic hypoaldosteronism represent respectively an excess and a deficiency of a circulating factor similar to frusemide capable of blocking renal tubular chloride transport.

Aldosterone↗
PubMed1984

Efferent role of ADH in CNS-induced natriuresis.

Ventriculocisternal perfusion (VCP) of artificial cerebrospinal fluid (CSF) was performed in pentobarbital-anesthetized dogs. Renal function was studied in protocols consisting of a 1-h experimental period in which the animals received either CSF with an elevated sodium concentration (300 mM, high Na) via VCP or antidiuretic hormone (ADH) intravenously, bracketed by 1-h control and recovery periods. High Na VCP caused an increase in plasma ADH measured by radioimmunoassay (to 176% of control) that coincided with a natriuresis (to 180% of control). In a second set of experiments, these changes in endogenous ADH were mimicked experimentally with intravenous infusions of synthetic ADH in animals receiving continuous VCP with normal sodium artificial CSF. The dose-response relationship between log ADH and urinary sodium excretion for the intravenous ADH experiments was not different from the relationship for those experiments in which ADH was elevated as a consequence of high Na VCP. These results suggest that ADH causes part, if not all, the natriuresis induced by high Na VCP.

Animals↗
PubMed1983

The relationship of adrenal gland iodomethylnorcholesterol uptake to zona glomerulosa function in primary aldosteronism.

Dexamethasone suppression adrenal scintiscans were performed on 37 patients referred for evaluation of primary aldosteronism (PA). Twenty-one had aldosterone-secreting adrenal adenoma (AA) and 16 had bilateral adrenal hyperplasia (BAH). The diagnosis of either AA or BAH was confirmed by adrenalectomy in 19 of 21 subjects with AA and by adrenal venous sampling in 15 of 16 patients with BAH. Biochemical parameters of PA were found in each patient while on both high (150 meq Na) and low salt (10 meq Na) intakes. Urinary aldosterone excretion values were 49.7 +/- 10.2 (+/- SEM) micrograms/day (range, 11.2-103.9) and 44.2 +/- 12.1 micrograms/day (range, 14.3-128.0) in AA patients on high and low salt intakes, respectively. In BAH patients, urinary aldosterone values were 29.1 +/- 2.6 micrograms/day (range, 10.0-55.0) and 47.7 +/- 9.0 micrograms/day (range, 23.0-102.0) on high and low salt intakes, respectively. A semioperator-independent computer algorithm was used to calculate adrenal gland uptake of [131I]6 beta-iodomethyl-19-norcholesterol (NP-59) in PA patients and in 7 patients with essential hypertension. NP-59 adrenal uptake values were 0.20 +/- 0.02%/dose (range, 0.03-0.72), 0.28 +/- 0.04% (range, 0.10-0.65), and 0.14 +/- 0.02%/dose (range, 0.08-0.30) in AA, BAH, and essential hypertension, respectively. A significant correlation was found between adrenal gland uptake of NP-59 and urinary aldosterone excretion in AA (r = 0.93; P less than 0.001) and BAH (r = 0.6; P less than 0.01) patients. These data confirm that adrenal gland accumulation of NP-59 while on dexamethasone suppression can be used to characterize abnormal zona glomerulosa function in PA, in addition to localizing AA and differentiating AA from BAH.

Adenoma↗
PubMed1983

Increased urinary vasopressin excretion in the DOCA-hypertensive pig.

A possible role for vasopressin in the development and/or maintenance of DOCA hypertension in pigs was studied. In control pigs mean arterial blood pressure (MABP), plasma lysine vasopressin (LVP) concentration, the 24-h urinary excretion of LVP (ULVPV) and plasma renin activity (PRA) did not change throughout the 30 days of the experiment. In DOCA-treated pigs MABP began to increase from the initial level of 95 +/- 2 mm Hg within 5 days and reached a level of 127 +/- 3 mm Hg between days 20-30 (P less than 0.01). At this time in the DOCA treated pigs, ULVPV increased threefold (P less than 0.05), although PLVP was unchanged and PRA was reduced to almost zero. After 30 days the pigs were fed a low sodium diet. This was without effect on MABP, PLVP and ULVPV in control pigs. However, in the DOCA-treated pigs, MABP fell from 133 +/- 2 to 112 +/- 6 mm Hg, accompanied by a 60% fall in ULVPV. PLVP was unchanged. Thus in DOCA-treated pigs, LVP appears not to be involved in the development of hypertension, but may be involved in its maintenance.

Animals↗
PubMed1983

Differential effects of DOCA on renal and gastrointestinal handling of sodium and potassium in pigs.

Young, male pigs eating standard pig chow, ad libitum, received approximately 170 mEq Na and 290 mEq K per day. Electrolyte intake, urinary and fecal electrolyte output, and plasma electrolyte levels were determined daily in 12 deoxycorticosterone acetate (DOCA)-treated pigs and in 6 control pigs. Daily Na and K balances (dietary intake - urinary + fecal output) were calculated. DOCA caused a reduction in urinary Na output from 1.53 mEq/kg/day to 0.57 mEq/kg/day during the first 48 hr following implantation. Escape from the renal sodium retaining effect of DOCA was complete within 3 days, with urinary Na output returning to pre-DOCA levels. Fecal Na output decreased from 0.65 mEq/kg/day during the preimplant period to 0.13 mEq/kg/day during the postimplant period. No escape from GI Na retention occurred by Day 15. Plasma Na rose to significantly higher levels by Day 15. Sodium balance was significantly elevated in DOCA-treated pigs for that first 48 hr postimplant. Urinary K output decreased from 3.50 mEq/kg/day to 1.74 mEq/kg/day during the first 2 days, but returned toward preimplant levels by Day 4. Fecal K output was increased for the first week, and thereafter returned to preimplant levels. Plasma K fell from 3.9 to 2.9 mEq/liter by Day 15. Potassium balance fell slightly in both experimental and control animals. No significant differences in potassium balance were present between the two groups. The control pigs showed no significant changes in plasma electrolyte concentration or in electrolyte balance. It is concluded that DOCA has differential effects on renal and gastrointestinal handling of electrolytes and that DOCA may induce an intracellular shift of potassium in pigs.

Animals↗
PubMed1983

Endocrine hypertension.

Many endocrine abnormalities may lead to hypertension. An awareness of these disorders is important for clinicians caring for hypertensive patients, as direct therapy of the endocrine abnormality is frequently successful in reversing the hypertension. All patients with hypertension should be screened for hypokalemia and hypercalcemia, but other screening tests should be performed only under specific circumstances. Biochemical diagnosis of the endocrine abnormality must be established before localization or visualization procedures are undertaken. Therapy of endocrine hypertension is disorder specific, and frequently rests upon surgical correction of the underlying disorder. Despite this, antihypertensive medications are effective in controlling hypertension in many instances.

Acromegaly↗
PubMed1981

Suppression of aldosterone by cyproheptadine in idiopathic aldosteronism.

To study the role of serotonin in regulating the release of aldosterone, we gave single, oral doses of cyproheptadine, an antiserotoninergic agent, to five normal volunteers with high aldosterone levels secondary to sodium deprivation and to 14 patients with aldosteronism (six with idiopathic aldosteronism due to bilateral adrenal hyperplasia and eight with adrenal adenoma). A diet containing 150 mmol of sodium was given to the patients with spontaneous aldosteronism, and one containing 10 mmol of sodium was given to the normal subjects, for three days before treatment and throughout the study. All subjects received dexamethasone, 2 mg daily. Serum aldosterone was measured with the subject in the recumbent position before cyproheptadine administration and at 30-minute intervals for two hours afterward. Serum aldosterone fell significantly (P less than 0.025) from the basal level in the patients with idiopathic aldosteronism due to hyperplasia. No fall was observed in the normal subjects or in the patients with adenoma. No changes were seen in renin activity, cortisol, sodium, or potassium, in any group after cyproheptadine. Suppression of aldosterone with cyproheptadine suggests a serotonin-mediated aldosterone-stimulating system. Hyperactivity of this system may be the cause of idiopathic aldosteronism associated with adrenal hyperplasia.

Adenoma↗
PubMed1981

The role of parmacologic manipulation in adrenal cortical scintigraphy.

Adrenal scintigraphy is a unique nuclear medicine procedure that provides noninvasive, functional information concerning the status of the adrenal cortex. The uptake of iodocholesterol, in addition to localizing adrenal cortical abnormalities, can be manipulate to focus on adrenal cortical dysfunction in either the aldosterone, cortisol, or androgenproducing portions of the adrenal cortex. The uptake of iodocholesterol correlates significantly with the abnormal secretion of cortisol in Cushing's syndrome, aldosterone in the model of adrenal zona glomerulosa function, and adrenal androgen secretion in hyperandorgenism. For these reasons, adrenal scintigraphy is an important diagnostic modality in the evaluation of adrenal cortical function.

Adrenal Cortex↗
PubMed1981

The effect of indomethacin on vasopressin-induced antidiuresis in man.

1. The effect of 3 days' treatment with indomethacin on the renal response to infused vasopressin was assessed in eight healthy volunteer subjects. 2. Indomethacin produced significant weight gain and an increase in serum potassium without a change in creatinine clearance. 3. Although indomethacin reduced maximum free water clearance in five subjects, the anti-diuresis produced by an incremental infusion of physiological amounts of vasopressin was no different whether indomethacin had been taken or not. 4. Indomethacin, in the dose we have used, is known to reduce prostaglandin production and we therefore conclude that endogenous prostaglandins do not inhibit the effect of physiological amounts of vasopressin on water clearance, which makes it unlikely that prostaglandins are important in the day-to-day modulation of response to vasopressin.

Adult↗