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Biomedical subjects

J Genest

Publications and source records attributed to J Genest.

At least 253 records · Page 14Linked to original sources
PubMed1983

Purification of three rat atrial natriuretic factors and their amino acid composition.

A natriuretic factor has been described in the specific granules of rat atria. We have purified three factors which seem to be low-Mr peptides. They have been purified by means of acid extraction, octadecyl Sep-Pak cartridges, and chromatography on Bio-Gel P-10, CM Bio-Gel A, Mono S and reverse-phase high-performance liquid chromatography columns. The factors contain 26, 31 and 33 amino acids and may have been partially degraded during isolation. They are all 3 biologically active and the shorter one is the most active with a specific activity of 450 000 units/mg.

Amino Acids↗
PubMed1983

Altered hormone sensitivity of adenylate cyclase in myocardial sarcolemma of renal hypertensive rats.

Adenylate cyclase activity was studied in the myocardial sarcolemmal membranes from sham-operated control and renal hypertensive rats (RHR). Basal adenylate cyclase activity was not significantly different in RHR as compared to control rats. The stimulation of adenylate cyclase by adenosine, epinephrine and norepinephrine was diminished in RHR, whereas dopamine-sensitive adenylate cyclase was almost completely abolished. The decreased responsiveness of adenylate cyclase to catecholamines was associated with a decrease in the Vmax. Furthermore, the stimulation of enzyme activity by F- and forskolin was also decreased. The data indicate that, in renal hypertension, the responsiveness of adenylate cyclase to various hormones and to agents (forskolin and F-) which do not act through receptors is impaired.

Adenylyl Cyclases↗
PubMed1983

Inhibition of corticotropin release in vitro by dexamethasone, aldosterone and spironolactone.

Dexamethasone, aldosterone and spironolactone inhibited the release of immunoreactive corticotropin (ACTH) from primary culture of the rat anterior pituitary cells. The steroids inhibited only the ACTH release stimulated by Pitressin and not the basal ACTH release by non-stimulated cells. On a molar basis, aldosterone appears to be the most efficient inhibitor of ACTH release while the effect of spironolactone is similar to the effect of dexamethasone. Simultaneous incubation with aldosterone and spironolactone inhibited the ACTH release to the same extent as spironolactone alone. This indicates that aldosterone's effect on ACTH release is also inhibited by spironolactone at the pituitary level.

Adrenocorticotropic Hormone↗
PubMed1983

Response of human aldosteronoma cells in culture to the N-terminal glycopeptide of pro-opiomelanocortin and gamma 3-MSH.

Cells were isolated from one of two adenomas from the adrenal cortex of a hypertensive patient with primary hyperaldosteronism. A primary culture of these cells responded with increased aldosterone secretion to gamma 3-MSH and human (residues 1-76) and porcine (residues 1-80) N-terminal peptides of pro-opiomelanocortin (POMC). EC50 was lowest for gamma 3-MSH, while maximal response was greater for both N-terminal peptides of POMC. We conclude that gamma 3-MSH derived from the N-terminal segment of POMC contains the active core of the aldosterone-stimulating activity of the N-terminal on these adrenal cells.

Adenoma↗
PubMed1983

Catecholamine glucuronidation: an important metabolic pathway for dopamine in the rat.

In the present study, we found that large quantities of dopamine (DA) glucuronide were present in rat cerebrospinal fluid (CSF), plasma, and urine, whereas the glucuronides of norepinephrine (NE) and epinephrine (E) were almost undetectable. The high urinary excretion of DA glucuronide was in a range comparable to that of homovanillic acid (HVA). Sulfates of DA, NE, and E were measurable in all three body fluids, but only in small quantities. The measured DA glucuronide was predominantly of endogenous origin, as the feeding of sucrose instead of routine diet did not reduce the urinary output of DA glucuronide. Adrenalectomy but not peripheral sympathectomy induced by chronic guanethidine injection substantially decreased plasma DA glucuronide concentrations, indicating that the adrenals serve as an important source of endogenous DA glucuronide. The data suggest that glucuronidation constitutes an important metabolic pathway for endogenous DA of central and peripheral origin in rats; this route, however, is exclusive to DA and appears to play a negligible role for NE and E.

Animals↗
PubMed1983

Role of the pituitary in the effects of tonin on adrenal secretion of the rat.

Chronically catheterized conscious rats were infused intravenously with tonin at 2.4 and 12 micrograms x kg-1 x min-1 for 2 h. Plasma aldosterone concentration (PAC) at the end of the experiment was 11.2 +/- 2.4 ng% in controls, 8.5 +/- 2.8 ng% in rats infused with tonin at the lower rate, and 26.2 +/- 3.6 ng% (p less than 0.01 vs. controls) in rats infused at the higher rate. Plasma corticosterone (PC) was significantly higher (p less than 0.05) in the group infused at the high rate while plasma renin activity (PRA) was significantly reduced in this group of rats. Plasma angiotensin II (AII) concentration was similar in all three groups. PAC was elevated after tonin infusion in the presence of AII blockade. PAC in conscious sodium-depleted rats infused with tonin was not significantly changed, but PRA was significantly reduced (p less than 0.01). In chronically hypophysectomized rats, PAC remained unchanged by tonin infusion. The failure of tonin to stimulate aldosterone in hypophysectomized animals indicates a role of a pituitary hormone (probably ACTH) in the effect of tonin on adrenal secretion.

Adrenal Glands↗
PubMed1983

Kallikrein concentration in submandibular glands of rats chronically treated with isoproterenol.

The effect of chronic beta-adrenergic stimulation with isoproterenol on the kallikrein content of rat submandibular gland was estimated by radioimmunoassay, by immunohistochemistry, and by analytical isoelectric focusing. Radioimmunoassays revealed that the kallikrein content of the submandibular gland was already significantly decreased after 6 days of treatment. After 21 days, the kallikrein content was 40 times lower and by 33 days an almost complete depletion was found. These findings were confirmed by immunohistochemistry. Analytical isoelectric focusing also showed that, after 33 days of treatment, the typical bands corresponding to the kallikrein isoenzymes of the submandibular gland had disappeared. These results indicate that kallikrein secretion is influenced by beta-adrenergic stimulation.

Animals↗
PubMed1983

Changes of catecholamines in central and peripheral tissues and in the urines of deoxycorticosterone--salt hypertensive rats.

The catecholamine concentrations in the urines and in the tissues of the kidney, heart, striatum, and hypothalamus of control rats and rats treated with deoxycorticosterone and salt for 2-week and 5-week periods were measured and compared. In 2-week-treated rats there were no changes in blood pressure and catecholamines. In 5-week-treated rats, the blood pressure increased from 117 +/- 5 to 152 +/- 5 mmHg (1 mmHg = 0.13 kPa) and there was an increase of urinary dopamine, norepinephrine, and epinephrine. The kidney and heart tissues of the hypertensive rats showed a decrease of norepinephrine while in the hypothalamus all three catecholamines were increased. These data suggest that dopamine and epinephrine may also be involved in the sympathetic dysfunction in deoxycorticosterone--salt hypertension. They demonstrate for the first time an increase of dopamine, norepinephrine, and epinephrine in the hypothalamus of deoxycorticosterone--salt hypertensive rats.

Animals↗
PubMed1983

Effect of a potassium-deficient diet on arterial blood pressure, plasma and tissue cations, and tissue norepinephrine in the hypertensive dog.

Chronic potassium deficiency in one-kidney one-clip hypertensive dogs significantly reduces blood pressure and plasma potassium, with a simultaneous increase in plasma renin activity. Tissue potassium concentration was decreased and tissue sodium concentration was increased in striated muscle and adrenal glands, which may suggest that the sodium-potassium pump was inhibited. In myocardium the sodium concentration was higher but the potassium concentration was not significantly lower than in control hypertensive dogs on normal diets. Arterial cation concentrations in the potassium-deficient group were not significantly different from those in the control group. Tissue norepinephrine concentration was higher in arteries from potassium-deficient animals, significantly so in the mesenteric and femoral arteries. The conclusion is that potassium deficiency may decrease blood pressure in the one-kidney one-clip hypertensive dogs by impairing the release of norepinephrine.

Animals↗
PubMed1983

Release of tonin and of kallikrein by perfused rat submaxillary gland.

The release of tonin and kallikrein was investigated in the venous effluent of the perfused rat submaxillary gland (SMG). The SMG was perfused through the common carotid artery after all branches except the SMG artery had been ligated. The venous outflow was collected from the SMG vein. The contralateral nonperfused gland was used as control. The infusion of isoproterenol increased tonin release without affecting its concentration in the SMG. Theophylline increases both tonin secretion and tonin concentration in the SMG. These results suggest that beta-adrenergic stimulation enhances tonin release by increasing synthesis in the SMG, and that these effects might be mediated by cAMP. The infusion of norepinephrine did not affect either tonin release or tonin concentration in the gland. Kallikrein release was significantly increased by norepinephrine, isoproterenol, and theophylline. However, whereas alpha-stimulation produced a significant decrease in kallikrein concentration in the stimulated SMG, beta-adrenergic and theophylline stimulation produced no significant changes in tissue kallikrein. These results suggest that alpha-adrenergic stimulation increases kallikrein release by depleting the enzyme from the gland, whereas beta-adrenergic stimulation might increase kallikrein release by stimulating its synthesis in the gland.

Animals↗
PubMed1983

3H-vasopressin binding to the rat mesenteric artery.

We investigated the binding of 3H-Arg8-vasopressin to membranes from rat mesenteric arteries. Specific binding of 3H-vasopressin was 60-75% of total binding. Binding at 22 C achieved a plateau at 30 min whereas at 4 C binding was significantly slower. Binding was reversible upon addition of 1 microM Arg8-vasopressin after 30 min of incubation. Scatchard analysis indicated a single class of high-affinity binding sites with an equilibrium dissociation constant of 5.1 +/- 0.6 nM and a total binding capacity of 91 +/- 12 fmol/mg protein. Competitive inhibition of 3H-Arg8-vasopressin binding showed an IC50 of 3 nM for Arg8-vasopressin, 14 nM for [I-(beta-mercapto-beta-beta-cyclopentamethylene-propionic, 4-valine, 8-D-arginine]-vasopressin, 31 nM for oxytocin, 52 nM for I-deamino-8-D-arginine-vasopressin, 0.1 microM for [I-deamino-penicillamine, 4-valine, 8-D-arginine]-vasopressin, and 0.8 microM for desglycinamide-deamino-Arg8-vasopressin. Unrelated peptides did not displace 3H-Arg8-vasopressin. We conclude that these binding sites possess characteristics of physiologically relevant vasopressin receptors in vascular smooth muscle of a resistance type vessel.

Animals↗
PubMed1983

Extrarenal angiotensin-forming enzymes.

There are two types of enzymes in tissues leading to angiotensin formation: a) those resulting in the formation of angiotensin I, such as renin and cathepsin D, the presence of which is now well established for brain tissue and b) Those leading to the direct formation of angiotensin II without the angiotensin I step, such as cathepsin G and tonin. Recent findings concerning tonin, a serine protease, are described: a) 80% of its amino acid sequence, b) its different characteristics from other serine proteases, from renin, cathepsin D and the angiotensin I converting enzyme, c) the activation of inactive renin, d) its involvement in the 1K-1C hypertensive rats, e) the demonstration of its presence in the distal tubular cells of the rat kidney, and finally, f) its presence in urine and the influence of age and of sodium intake on its urinary excretion.

Amino Acids↗
PubMed1983

Volume hormones and blood pressure.

Four major volume hormones may be involved in human hypertension: aldosterone, arginine vasopressin, inhibitors of NA+/K+ ATPase activity, and the natriuretic factor from specific granules of atrial cardiocytes. Because there is no increase in either blood or extracellular fluid volumes, or total exchangeable sodium in patients with mild essential hypertension, the mechanism of action of the volume hormones must be through their effect on sodium regulation, intracellular concentration, and the related enhancement of arteriolar sensitivity and responsiveness. A review of the evidence relating these hormones to blood pressure regulation emphasizes inhibitors of Na+/K+ ATPase activity, and the potent natriuretic and diuretic factor found in homogenates of rat atria.

Aldosterone↗
PubMed1983

Conjugation patterns of endogenous plasma catecholamines in human and rat. A new specific method for analysis of glucuronide-conjugated catecholamines.

Plasma free, sulfoconjugated, and glucuronoconjugated CAs were determined radioenzymatically before and after hydrolysis. CA sulfates and glucuronides were hydrolyzed by sulfatase and Ketodase, respectively. Total CA conjugates were deconjugated by acid lyophilization. On the basis of data obtained from systematical studies on these methods, the conjugation patterns of endogenous plasma CA in human and rat have been qualitatively and quantitatively identified. The results show that (1) in human plasma, sulfation is the sole conjugation mode for DA, NE, and E; (2) in rat plasma, sulfation also occurs in DA, NE, and E but the quantities of the sulfates are small, whereas glucuronidation predominates in DA and occurs exclusively in DA but not in NE and E; (3) in both species, conjugation is preferential for DA rather than NE and E. In this study, a new specific method for analysis of glucuronoconjugated CA has been developed.

Animals↗