PubMed Health⌕ Search

Biomedical subjects

R Grekin

Publications and source records attributed to R Grekin.

12 recordsLinked to original sources
PubMed2001

Spironolactone reduces cerebral infarct size and EGF-receptor mRNA in stroke-prone rats.

Remodeling of the cerebral vasculature contributes to the pathogenesis of cerebral ischemia. Remodeling is caused by increased smooth muscle proliferation and may be due to an increase in the responsiveness of vascular cells to epidermal growth factor (EGF). Aldosterone is a risk factor for stroke, and the literature suggests it may play a role in increasing the expression of the receptor for EGF (EGFR). We hypothesized that mRNA for the EGF-stimulated pathway would be elevated in the vasculature of stroke-prone spontaneously hypertensive rats (SHRSP) and that this and experimental ischemic cerebral infract size would be reduced by aldosterone inhibition with spironolactone. We found that spironolactone treatment reduced the size of cerebral infarcts after middle cerebral artery occlusion in SHRSP (51.69 +/- 3.60 vs. 22.00 +/- 6.69% of hemisphere-infarcted SHRSP vs. SHRSP + spironolactone P < 0.05). Expression of EGF and EGFR mRNA was higher in cerebral vessels and aorta from adult SHRSP compared with Wistar-Kyoto rats. Only the expression of EGFR mRNA was elevated in the young SHRSP. Spironolactone reduced the EGFR mRNA expression in the aorta (1.09 +/- 0.25 vs. 0.56 +/- 0.11 phosphorimage units SHRSP vs. SHRSP + spironolactone P < 0.05) but had no effect on EGF mRNA. In vitro incubation of aorta with aldosterone +/- spironolactone produced similar results, suggesting a direct effect of aldosterone. Thus spironolactone may reduce the size of cerebral infarcts via a reduction in the expression of the EGFR mRNA, leading to reduced remodeling.

Aldosterone↗
PubMed1994

Interference by spironolactone on adrenocortical scintigraphy and other pitfalls in the location of adrenal abnormalities in primary aldosteronism.

A case of primary aldosteronism is presented in which the CT scan was initially misleading, adrenocortical scintigraphy was rendered inaccurate by pharmacological interference of spironolactone, and selective adrenal venous sampling of aldosterone was technically difficult. When dexamethasone suppression adrenocortical scintigraphy was performed with attention to technical detail and exclusion of interference by spironolactone, the causative lesion was scintigraphically demonstrated. This finding was confirmed by the results of venous sampling and the correctly located tumor removed.

Adosterol↗
PubMed1986

Role for aldosterone in blood pressure regulation of obese adolescents.

To determine the role of aldosterone in the regulation of blood pressure (BP) in obese adolescents, supine and 2-hour upright plasma renin activity (PRA), and aldosterone and cortisol were measured in 10 nonobese and 30 obese adolescents before and after a 20-week weight loss program. The obese adolescents had significantly higher supine and 2-hour upright plasma aldosterone concentrations (17 +/- 8 vs 6 +/- 2 ng/dl [p less than 0.01 supine obese vs nonobese] and 30 +/- 11 vs 14 +/- 8 ng/dl [p less than 0.01 2-hour upright]). Although PRA was not significantly different between the 2 groups of children, a given increment in PRA produced a greater increment in aldosterone in the obese adolescents. In addition, obese subjects had a significantly increased mean BP (93 +/- 12 vs 74 +/- 8, p less than 0.005) and a weak correlation between BP and plasma aldosterone concentration. Compared with an obese control group, weight loss resulted in a significant decrease in plasma aldosterone (p less than 0.01) without an associated decrease in PRA. After weight loss there was also a significant decrease in the slope of the posture-induced relation between PRA and aldosterone. In addition to weight loss being associated with a significant decrease in BP (p less than 0.01), there was a significant correlation between the change in plasma aldosterone and the change in mean BP (r = 0.538; p less than 0.002 change in upright aldosterone vs change in mean BP). Obese adolescents have an increased plasma aldosterone concentration that may be important in the regulation of their BP.

Adolescent↗
PubMed1986

Neurohumoral activation during exercise in congestive heart failure.

Neurohumoral factors were assessed in 14 subjects with chronic, stable New York Heart Association functional class II or III congestive heart failure and nine comparably aged normal subjects at rest and during moderate (50 W) and strenuous (100 W) upright exercise. Heart failure was associated with elevated plasma renin activity and plasma antidiuretic hormone (ADH) concentrations at rest. However, plasma renin activity almost doubled (from 4.7 +/- 0.6 to 8.4 +/- 1.1 ng/ml per hour) during strenuous exercise in subjects with heart failure, and changed only minimally in normal control subjects. Plasma ADH concentration did not change during exercise in the presence of heart failure, but rose in normal subjects during strenuous exercise to levels comparable to those of subjects with heart failure. Similar plasma osmolality values were present in both groups. Circulating norepinephrine concentrations were insignificantly elevated by heart failure both at rest and during exercise, and plasma epinephrine concentrations were similar. These findings suggest independent neurohumoral activation during exercise in the presence of congestive heart failure, with predominant activation of the renin-angiotensin-aldosterone axis.

Adult↗
PubMed1983

Hydrogen ion secretion by the rat distal nephron: adaptation to chronic alkali and acid ingestion.

Isolated rat kidneys perfused at a low bicarbonate concentration were subjected to increased rates of buffer excretion, provided as creatinine, in order to examine the maximal hydrogen ion secretory capacity of the distal nephron. Preliminary experiments with kidneys from normal rats indicated that the quantity of hydrogen ion that titrated creatinine from urine pH to a pH of 6.0, designated TA-pH 6.0, provided an index of net hydrogen ion secretion by a functional segment of the distal nephron. With this technique the response of distal nephron hydrogen ion transport to ingestion of both acid and alkali loads was examined. Perfused kidneys from rats with chronic metabolic acidosis, produced by drinking 1.5% NH4Cl for 3-5 days, excreted urine with a lower pH and higher total titratable acid and TA-pH 6.0 than appropriate controls. Perfused kidneys from rats that ingested NaHCO3 for 7 days exhibited a higher urine pH and lower rates of total titratable acid and TA-pH 6.0 than controls. By contrast, kidneys from rats acutely tube-fed NaHCO3 3 h prior to study showed no change in urinary acidification parameters. Thus, chronic ingestion of an acid load stimulates, and chronic ingestion of an alkali load inhibits, the intrinsic hydrogen ion secretory capacity of the rat kidney at a distal nephron site. This intrinsic adaptation of the hydrogen ion transport mechanism is not secondary to changes in aldosterone because rats that ingested NaHCO3 chronically had higher plasma aldosterone levels than controls.

Acclimatization↗
PubMed1978

Adrenal scintigraphy in low renin essential hypertension.

Adrenal scintigraphy was performed on 23 patients with low renin essential hypertension (LREH). After baseline scintigraphy was shown not to be helpful, 13 of these 23 patients underwent dexamethasone suppression adrenal scintigraphy. Four adrenal imaging patterns were observed: unilateral imaging with adenoma; bilateral early or late imaging with hyperplasia; no uptake with normal adrenals. These imaging patterns were shown to be predictive of the individual patient's response to spironolactone administration of functional adrenal cortical abnormalities in LREH supplies direct evidence for the hypothesis that LREH has an adrenal mineralocorticoid etiology.

Adenoma↗
PubMedDate not supplied

Sympathetic inhibition with methyldopa in heart failure.

The hypothesis that withdrawal of increased sympathetic activity may be beneficial in heart failure was tested by administration of the centrally acting adrenergic inhibitor methyldopa. Fourteen subjects with chronic, stable New York Heart Association Functional Class 2 or 3 heart failure receiving digitalis and diuretics were randomized to methyldopa (n = 8) 500-1000 mg daily or placebo (n = 6). Clinical, hemodynamic, neurohumoral, and platelet alpha 2-receptor effects were studied after chronic (3 weeks) administration. Sympathetic inhibition did not alter symptom status or exercise duration but reduced plasma norepinephrine concentration during exercise and permitted the same level of exercise to be attained at a lower pressure-rate product, indicating reduced myocardial oxygen consumption. Left ventricular ejection fraction and stroke volume tended to increase, and systemic vascular resistance tended to decrease during exercise after methyldopa administration, suggesting enhanced vasodilation. Upright plasma renin activity increased from 8.2 +/- 2.2 to 13.3 +/- 3.0 ng/nl/h (p = 0.03) after methyldopa, but plasma antidiuretic hormone concentration changed insignificantly. In a subset of patients, platelet alpha 2-receptor density and affinity were unaltered. Renal function was also unchanged. Thus, sympathetic inhibition induced by methyldopa in selected patients with chronic, stable heart failure does not worsen symptom status or exercise performance, and may produce a beneficial effect by withdrawal of excess sympathetic activity with reduction of plasma norepinephrine levels.

Adult↗
PubMedDate not supplied

Role of cardiopulmonary mechanoreceptors in ADH release in normal humans.

Although animal studies have shown that cardiopulmonary receptors regulate the release of antidiuretic hormone (ADH), human studies have produced conflicting results. Consequently, we studied 17 normal healthy men to determine the ADH response to selective unloading (decreased stretch) of cardiopulmonary low-pressure receptors by thigh cuff inflation in the supine position. Thigh cuff inflation of 30 to 40 mm Hg decreased the central blood volume and right atrial pressure (cardiopulmonary receptor load), while mean arterial pressure and pulse pressure were unchanged (arterial baroreceptor load). Thigh cuff inflation to this level did not alter plasma osmolality or cardiac output. Plasma ADH increased an average of 67% (p less than 0.01) following thigh cuff inflation compared to the preceding supine baseline. After thigh cuff deflation (n = 6), the ADH decreased toward preinflation values. We conclude that selective unloading of the cardiopulmonary receptors in humans increases plasma ADH levels.

Adolescent↗