Mechanisms of hypertension in obesity.

We conclude that the following may explain the rise in blood pressure with obesity and the subsequent fall in blood pressure (Fig. 2): (1) An increase in calories, protein, or carbohydrate leads to an increase in plasma catecholamines, sympathetic nervous system activity, and insulin secretion. (2) These factors, in turn, lead to increased renal sodium retention and stimulation of the renin-aldosterone system which, in turn, leads to: (3) An increased cardiac output with an inability to appropriately adjust the peripheral resistance to maintain normotension with resultant hypertension.

A kinetic study of cation transport in erythrocytes from uremic patients.

We previously described in red blood cells (RBCs) from uremic patients on dialysis a reduction in sodium (Na) efflux through the Na, potassium (K) cotransport system (Na,K CoT) while Na efflux through the Na,K pump was normal. We then examined Na efflux in fresh cells and in cells loaded to obtain one level of intracellular sodium (Nai) concentration at about 25 mmol/liter cell. In the present study we used similar cation flux methodology to examine the kinetics of cation efflux through the Na,K pump and Na,K CoT in uremic patients on dialysis.

Kinetic analysis of erythrocyte Na+-K+ pump and cotransport in essential hypertension.

Alterations in red blood cell (RBC) Na+-K+ pump and Na+-K+ cotransport have been described in essential hypertension. We evaluated Na+-K+ pump and cotransport in 30 hypertensive and 26 normotensive subjects subdivided by race and family history of hypertension using an improved method to examine the kinetics of Na and K effluxes. RBCs were Na-loaded by the nystatin method to five different levels of internal Na with pump determined as ouabain-sensitive Na efflux and cotransport as furosemide-sensitive Na and K efflux.

Cyclosporin A-induced hyperreninemic hypoaldosteronism. A model of adrenal resistance to angiotensin II.

We studied the effects of cyclosporin A on the renin-aldosterone axis in Sprague-Dawley rats. Two weeks of intragastric administration of cyclosporin A (5 mg/kg/day or or 20 mg/kg/day) resulted in large increases in plasma renin concentration (23 +/- 5, 70 +/- 12, and 79 +/- 11 ng/ml/hr in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively), with no parallel increments in plasma aldosterone. In vitro angiotensin II (ANG II)-stimulated aldosterone secretion by zona glomerulosa cells obtained from cyclosporin A-treated rats was also reduced (4.

Effect of high calcium intake on pressor responsivity in hypertensive rats.

Some proposed mechanisms for the hypotensive effect of high calcium intake involve reduction in vascular responsivity. To assess the effect of dietary calcium on vascular responsivity, spontaneously hypertensive rats (SHR) were placed on normal (N-Ca; 0.4%) or high (H-Ca; 2.

Diminished aldosterone responses to angiotensin II and adrenocorticotropin in hypocalcemic subjects: restoration of responsiveness with normocalcemia.

ACTH-, angiotensin II (AII)-, and K+-mediated aldosterone responses in vitro are dependent on extracellular and intracellular Ca concentrations. This study examined in vivo the relationship of changes in ambient serum calcium (serum Ca) to ACTH- and AII-mediated aldosterone release in hypoparathyroid subjects. Plasma aldosterone (PA) responses to graded dose infusions of ACTH and AII were examined in hypoparathyroid (HypoPTH) patients before (n = 8) and after correction of hypocalcemia (n = 6) and compared to responses in 20 normotensive normocalcemic subjects.

The chances of false negative results in conventional toxicology studies with rats.

Data from conventional rat toxicology studies from 2 centres are used to estimate the coefficients of variation of organ weights, haematology and blood chemistry characteristics commonly measured in such studies. Charts, based on simple statistical formulae, are provided which enable this information to be used to indicate the probability of failing to detect a treatment effect of a given magnitude as statistically significant. The results, for a study with 20 rats/treatment group, when the treatment causes a change of 10% in the characteristic, indicate wide variability in the false negative error rate.

Comparison of enalapril and thiazide diuretics in the elderly hypertensive patient.

One hundred seventy-four patients, 65 years of age or older, entered a double-blind, seven-center, 16-week, controlled study to compare the effects of enalapril and hydrochlorothiazide (HCTZ) in an elderly hypertensive population. Sixty-eight percent of the patients were men, 32% were women. Thirty-two percent of the patients had isolated systolic hypertension.

Evidence for dopaminergic binding sites in the human adrenal cortex.

Dopamine may be a modulator of aldosterone secretion in man. Whether this effect is extraadrenal or is exerted directly at the adrenal gland via local dopaminergic receptors remains uncertain. This study examined the possibility that dopaminergic binding sites exist in the human adrenal cortex using [3H]spiperone, a butyrophenone with high affinity for dopaminergic receptors of the D2 subtype.

Augmented aldosterone and insulin responses to potassium infusion in dogs with renal failure.

The present study examines acute potassium-induced insulin and aldosterone responses in renal failure, and the role of chronic dietary potassium intake in modifying these acute responses. Plasma aldosterone (PA) and insulin (IRI) responses to acute KCl infusion were examined in control and remnant kidney dogs on two potassium intakes. Dogs (N = 8) received the KCl infusions after 10 days of a 60, and then 10 days of a 200, mEq daily potassium intake during control and after surgical-induced renal failure (CRF).

The sympathetic nervous system in essential hypertension.

Enhanced activity of the sympathetic nervous system (SNS) could contribute to essential hypertension (EH). Results of over 80 studies measuring norepinephrine (NE) in EH patients show that only a minority of younger EH patients have elevated plasma NE. Younger EH patients also have increased renal NE spillover and elevated 24-hour NE levels.

Low-dose captopril in mild to moderate geriatric hypertension.

The safety and efficacy of captopril in geriatric patients with mild to moderate hypertension was examined in an eight-week multicenter study of 99 patients. Following a placebo period, patients were treated with captopril 25 mg twice daily. Patients who were uncontrolled after two weeks of active therapy were randomized to either captopril 25 mg plus hydrochlorothiazide 15 mg or captopril 50 mg twice daily.

Altered red cell sodium transport in hypoparathyroidism: relation to serum calcium.

We studied Na transport in red blood cells (RBC) from six patients with hypoparathyroidism (HYPO; 3 postsurgical and 3 idiopathic) and 13 normal subjects. In HYPO, the effect of treatment-induced increases in serum Ca2+ on RBC Na transport also was examined. Na efflux mediated by the ouabain-sensitive Na,K pump and furosemide-sensitive Na,K cotransport (CoT) was examined by flux methodology in RBCs Na loaded to 5 levels of intracellular Na (Nai; 5-90 mM/liter cells) by the p-chloromercuribenzene method.

Sodium transport in red blood cells from dialyzed uremic patients.

Studies on red blood cell (RBC) sodium (Na) transport in chronic renal failure have described abnormalities in the ouabain-sensitive Na, K pump. We now report Na transport in RBC using cation flux methodology, measuring both the ouabain-sensitive Na, K pump and the ouabain-insensitive Na, K cotransport (CoT) and Na, lithium (Li) countertransport (CTT) in 28 subjects on hemodialysis, eight subjects on chronic ambulatory peritoneal dialysis (CAPD) and 29 control subjects. Intracellular cation content and passive permeability of Na were also examined.

Homeostatic fragility in the elderly.

Age-related alterations in adaptation capacity to physiologic changes in physical workload, posture, and water and electrolyte metabolism are reviewed in this article. Other than the increased prevalence of disease in the elderly, normal aging is associated with changes in hormonal secretion patterns, tissue sensitivity to hormones, control of breathing, sleep, and renal function that make this population particularly vulnerable. Orthostatic hypotension, sleep apnea, hypernatremia, hyponatremia, and hyperkalemia, as well as other conditions, are discussed in light of these changes.

Dopaminergic binding and inhibitory effect in the bovine adrenal zona glomerulosa.

Dopaminergic mechanisms may be involved in the regulation of aldosterone secretion in humans and in the rat. Whether these effects are indirect or are exerted directly at the adrenal level has not yet been resolved. We now report the identification of dopaminergic binding sites in the bovine adrenal zone glomerulosa using [3H]spiperone, a butyrophenone with high affinity for D2 dopamine receptors.

Myelin basic protein-specific protein methylase I activity in shiverer mutant mouse brain.

Myelin basic protein (MBP)-specific protein-arginine N-methyltransferase (protein methylase I) activity in homozygous shiverer (shi/shi) mutant mouse brain is significantly higher than in the normal littermate brain at the onset of myelination. While the enzyme activity (expressed as pmol of S-adenosyl-L-[methyl-14C]methionine used/min/mg enzyme protein) increases coincidently during the period of myelination in the normal brain (15-18 days of age), it decreases significantly in the mutant brain during this period of time. These results are in contrast to those found with another dysmyelinating mutant, jimpy (jp/Y) mice, in which the enzyme activity in the mutant brains is similar to that in the normal animals but remains unchanged during the myelination process.

Two histone H1-specific protein-lysine N-methyltransferases from Euglena gracilis. Purification and characterization.

Two forms of a histone H1-specific S-adenosylmethionine:protein-lysine N-methyltransferase (protein methylase III) have been purified from Euglena gracilis 48- and 214-fold, respectively, with yields of 3.4 and 4.6%.

Purification and characterization of enzymes from Euglena gracilis that methylate methionine and arginine residues of cytochrome c.

Two forms of cytochrome c-specific methyltransferases from Euglena gracilis were purified approximately 100- and 50-fold, respectively, using DEAE-cellulose and gel-filtration chromatography. The methylation product of enzyme I was identified as S-methylmethionine and that of enzyme II as NG-monomethylarginine. Both enzymes were located in the cytosol and exhibit maximum activity at pH 7.

Observations on the "cascade" of Na-K-ATPase inhibitory and digoxin-like immunoreactive material in human urine: possible relevance to essential hypertension.

Previous investigations have demonstrated an increased amount of a sodium pump inhibitor (N.H.) in plasma from humans with essential hypertension and from animals with various forms of experimental hypertension.

Enhanced 24-hour norepinephrine and renin secretion in young patients with essential hypertension: relation with the circadian pattern of arterial blood pressure.

This study examines the possibility that 24-hour differences in blood pressure (BP) regulation between hypertensive and normotensive subjects is related to changes in 24-hour secretory patterns in circulating pressor hormones. Nine young subjects with normal BP and 9 patients with essential hypertension (EH) were studied during 24-hour recumbency. Every 20 minutes samples were taken to determine plasma norepinephrine (NE) levels and plasma renin activity (PRA).

Defective renal prostaglandin synthesis in hypertensive patients with morbid obesity.

Renal prostaglandin synthesis in 36 obese hypertensive patients was estimated from measurements of 24-hour urinary prostaglandin E2 (PGE2) excretion rates. PGE2 was measured by radioimmunoassay using Dray antiserum prior to and 1 week after starting a fast supplemented by 320 cal derived from 30 g of carbohydrate, 45 g protein, and 2 g essential fatty acids. Sodium intake was 120 mEq daily or less.