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Biomedical subjects

J R Lymangrover

Publications and source records attributed to J R Lymangrover.

14 recordsLinked to original sources

Rat adrenal zona fasciculata cell electrophysiological responses to ACTH and gamma-MSH vary with age.

A comparison was made of the resting membrane potential (MP) as well as the MP responses to K+, ACTH and gamma-MSH of superfused adrenocortical, zona fasciculata cells from young (Y) and old (O) male rats. The resting MP of these cells did not vary with age. However, the MP responses to altered extracellular [K+] varied significantly with age. A prolonged biphasic depolarization was observed following ACTH administration; these responses were significantly reduced in O cells. In contrast, stimulation with gamma-MSH did not consistently elicit depolarization in the Y but caused a consistent and prominent depolarization in O cells. These findings suggest that aging is associated with changes in primary membrane events which could explain the reduced ACTH-stimulated steroidogenesis associated with age. Elevated cellular responses to gamma-MSH may contribute to a maintenance of, or increase in, circulating corticosterone levels in aged rats.

Adrenal Cortex

Direct power-frequency electric field effects on mammalian endocrine tissue.

A number of studies have investigated the in vivo biological effects of power-frequency electric fields (EF). Direct effects of EF on mammalian tissues, however, have rarely been reported. We now report that a 60-Hz EF can directly enhance the steroidogenic response of superfused rat adrenocortical tissue. The EF did not influence basal steroidogenic activity, however, the corticosterone response to 10 mU of ACTH was almost doubled by an unperturbed 1000 kV/m EF during the initial 2 hr of exposure and was enhanced fourfold by 5.5 to 7 hr of exposure with a 10 kV/m EF. Other EF intensities (e.g., 5 and 100 kV/m) were without effect at these times. Turning the 1000 kV/m EF on and off at 30-min intervals did not influence the initial enhanced steroidogenic response but did cause an additional two- to threefold elevation in the response following 5.5-7 hr of exposure. It is not clear what EF exposure parameters or mechanisms were primarily responsible for these bioeffects, but it appears that direct exposure of mammalian endocrine tissue to a 60-Hz EF is capable of significantly influencing important cellular processes.

Adrenal Cortex

Chronic 60-Hz electric field exposure-induced subtle bioeffects on hematology.

The effects of 120 days of high-intensity (80-kV/m) 60-Hz electric field exposure on hematologic constituents were investigated using a three-generation design including 135 field-exposed and 135 sham-exposed male Sprague-Dawley rats. Statistical tests performed included the multivariate analysis of variance, the univariate analysis of variance, and tests of simple effects. Total white cell count, lymphocyte count, and eosinophil count were significantly lower in field-exposed subjects; however, none of the red cell parameters differed significantly. The observed hematologic variations related to the exposure of a high-intensity electric field are consistent with those observed in animals responding to a mild stressor.

Analysis of Variance

Pressor and cardioaccelerator effects of gamma MSH and related peptides.

We have recently demonstrated that the hypertensinogenic and natriuretic actions of ACTHI-39 can be found in a non-steroidogenic fragment of ACTH, ACTH4-10. These effects of ACTH or ACTH4-10 may be due to their ability to act as weak agonists of gamma MSH. gamma MSH is found in the 16K N-terminus of pro-opiocortin, and contains a sequence analogous to ACTH4-10, gamma MSH3-9. We investigated the cardiovascular effects of gamma 2MSH, gamma MSH3-9, and sterically restricted analogs of ACTH4-10. The results indicate that gamma MSH3-9, had essentially the same activities as ACTH4-10. The addition of five other amino acid residues to gamma MSH3-9 (gamma 2MSH) resulted in significant enhancement of pressor and cardioaccelerator activity. Steric restriction of the ACTH4-10 sequence by the substitution of a D-Phe in place of an L-Phe residue in position #7, or cyclization of the peptide by a half-Cys4, half Cys10 intramolecular disulfide-bridge derivatization, resulted in increased cardiovascular activities. Based on these data, the cardiovascular actions of ACTH4-10, gamma MSH3-9, and gamma 2MSH are predicted to be due to the assumption of a reverse-turn three-dimensional structure. The additional residues in gamma 2MSH appear to specifically enhance the cardiovascular activities of gamma MSH3-9. The results suggest the existence of a new class of hypophyseal peptides with cardiovascular activities, which require the assumption of a defined three-dimensional structure.

Adrenocorticotropic Hormone

Gamma-2MSH is natriuretic in the rat.

Previous reports suggest that peptides containing an amino acid sequence similar to that of ACTH-(4-10) increased Na excretion in the rat. gamma 2MSH contains such a sequence. An in vivo rat bioassay for natriuretic factors was employed to demonstrate the natriuretic action of gamma 2MSH. A significant natriuretic effect was observed, with a peak response 30-50 min following the bolus injections of 0.64, 6.4 or 64 pmol, but not with smaller or larger amounts of gamma 2MSH. A kaliuretic and diuretic action of gamma 2MSH was not consistently evident. gamma MSH may represent an endogenous compound involved in the physiological regulation of Na excretion.

Animals

Cardiovascular investigations of an endogenous digoxin-like factor.

A circulating factor with digoxin immunoreactivity has been demonstrated. Elevated levels of this substance appear to be present after volume expansion and salt loading, and in some forms of hypertension. The potentially causative role for this factor in hypertension can be demonstrated by the normalization of blood pressure after antidigoxin antibody infusions in low-renin and sodium-dependent hypertension. The possibility that renal excretory defects may be the initiating event to elevate endogenous digoxin is suggested by studies with normotensive humans and monkeys with renal disease. In the latter case cardiovascular deficits were noted that were analogous to those detected in renal hypertensive monkeys with elevated endogenous digoxin. Considered together, these results suggest the existence of a natriuretic and hypertensive substance that plays a role in body fluid homeostasis and blood pressure regulation.

Animals

Natriuretic peptides derived from pro-opiocortin.

Natriuresis in response to hypertonicity, volume loads, or high sodium diets has been proposed to be mediated by the release of a humoral factor(s), and controlled by the central nervous system. We have determined that the natriuretic activity of ACTH or alpha MSH resides in a common sequence, ACTH(4-10)/alpha MSH(4-10). Steric restriction of this peptide by replacement of an L-Phe residue with a D-Phe produced a superagonist. Gamma-2 MSH is a peptide derived from the 16K N-terminus of pro-opiocortin, which contains an ACTH(4-10)-like sequence. The natriuretic effect of gamma-2 MSH was maximal between 0.64 pmole to 64 pmole. Doses greater than 128 pmole produced no significant effects on renal sodium excretion. The regulated release of gamma MSH peptides may contribute to CNS regulation of renal sodium excretion.

Adrenocorticotropic Hormone

Sympathetic nervous system mediation of acute cardiovascular actions of gamma 2-melanocyte-stimulating hormone.

Peptides of the pro-opiocortin class produce pronounced cardiovascular and natriuretic actions. We have investigated the acute cardiovascular effects of one of the most potent members of this class, gamma 2-melanocyte stimulating hormone (gamma 2-MSH), in rats. Pressor actions of gamma 2-MSH administered systemically were eliminated by ganglionic blockade with chlorisondamine. Peripheral cholinergic blockade failed to affect either the pressor or cardioaccelerator responses to gamma 2-MSH. Administration of gamma 2-MSH (2.0-10.0 micrograms) produced vasoconstriction primarily in the mesenteric and hindlimb vascular beds, while the renal bed showed little response. Infusions of phenylephrine produced pressor responses similar to those found with gamma 2-MSH, which were accompanied by a decrease in heart rate and vasoconstriction in the mesenteric and renal vascular beds. Hemodynamic changes produced by gamma 2-MSH and phenylephrine were blocked or attenuated by alpha 1-adrenergic receptor blockade with prazosin. Direct injection of gamma 2-MSH into the renal artery produced an acute renal vasoconstriction that was not attenuated by alpha 1-adrenergic or ganglionic blockade. These findings and the results of previous publications are consistent with the hypothesis that gamma 2-MSH may produce a centrally mediated activation of the sympathetic nervous system, have direct vasoconstriction actions on the renal vasculature, and inhibit baroreceptor function to produce an increase in blood pressure without an accompanying bradycardia.

Adrenergic alpha-Antagonists