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W Nowaczynski

Publications and source records attributed to W Nowaczynski.

At least 19 recordsLinked to original sources
PubMed1989

Digoxin-like immunoreactivity, displacement of ouabain and inhibition of Na+/K+ ATPase by four steroids known to be increased in essential hypertension.

An endogenous digoxin-like immunoreactive substance(s) (DLIS, "endoxin") may be of significance in the etiology of essential hypertension (EH). Progesterone, dehydroepiandrosterone sulphate (DHEA-S), 11-deoxycortisol and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), four steroids known to be increased in essential hypertension, were found to have digoxin-like immunoreactivity at levels 1,000 times higher than physiological concentrations. Of these steroids, progesterone and 18-OH-DOC were the most efficient in displacing 3H-ouabain from canine kidney Na+/K+ ATPase whereas progesterone and 11-deoxycortisol were the most potent inhibitors of this enzyme's activity. Although 18-OH-DOC and DHEA-S cross-reacted with digoxin-specific antibodies, their ability to inhibit Na+/K+ ATPase activity was minimal. Although it is concluded that these steroids may contribute to DLIS as isolated from hypertensive patients, it is unlikely that they would be of physiological significance in the etiology of EH unless they were to accumulate and act synergistically within vascular wall smooth muscle tissues.

Animals↗
PubMed1988

Plasma cortisol and corticosteroid-binding globulin in essential hypertension.

Plasma concentration of cortisol, total CBG-binding capacity, and blood pressure were measured in control subjects (n = 171), patients with essential hypertension (EH; n = 210) and their first-degree normotensive (NR; n = 84) or hypertensive (HR; n = 66) relatives. Mean (+/- SD) plasma cortisol was significantly (p less than 0.001) decreased in EH (10.1 +/- 4.3 g/dl) patients and HR (11.7 +/- 4.1). Plasma cortisol in NR did not differ from control values (14.3 +/- 4.5) but the distribution of individual values covered the entire control-EH (14.6 +/- 5.5) range. Mean (+/- SD) CBG-binding capacity was significantly (p less than 0.001) lower in EH (14.4 +/- 3.0), NR (17.5 +/- 2), HR (17.6 +/- 2.2) as compared to controls (20.9 +/- 2.1), indicating that the decline in EH and in most relatives was mainly in plasma CBG-bound cortisol. The plasma CBG-binding capacity for cortisol was significantly negatively correlated with mean arterial pressure (MAP) in both controls (p less than 0.001) and NR (p less than 0.01) but not in either HR (r = 0.02) or never-treated EH patients. Total afternoon plasma aldosterone was higher (p less than 0.01 vs. controls) in 93 untreated EH patients (11.2 +/- 4.8 ng/dl) than in either 161 first-degree relatives (8.1 +/- 3.4 ng/dl) or 117 controls (7.6 +/- 3.5 ng/dl). The respective aldosterone-binding globulin (ABG) binding capacities for aldosterone were 21.2 +/- 6.7, 20.1 +/- 9.3 and 9.8 +/- 4.0%. In all these subjects taken together, there was a positive correlation between MAP and ABG-binding capacity (r = 51; p less than 0.001). The association of reduced plasma cortisol and decreased CBG binding capacity in EH may be closely related to altered steroid metabolism, which may be partly explained by an abnormality resembling a relative deficiency in adrenal 17 alpha- and 11 beta-hydroxylation. In some EH patients, hypertension may be the result of the ineffectiveness of plasma cortisol in preventing slightly elevated endogenous ACTH levels leading to an increase in ACTH-sensitive steroids.

Adolescent↗
PubMed1987

Absence of plasma protein binding of aldosterone in normal and estrogen-treated rabbit.

In experiments on direct effects of prolonged administration of estrogen on In experiments on direct effects of prolonged administration of estrogen on mean arterial pressure (MAP) and plasma corticosteroid-binding variables in the rabbit the following observations were made. Estrogen had no effect on MAP but resulted in a nonsignificant stimulation of total plasma corticosteroids and a marked increase in corticosteroid-binding globulin (CBG) binding capacity which increased from a control value of 18.8 +/- (SD) 1.2 micrograms/100 ml to 28.1 +/- 2.3 micrograms/100 ml (p less than 0.001) following the administration of estrogen for the first 21 days (approx. 10 micrograms/day) and then further to 31.4 +/- 2.8 (p less than 0.001 vs. control values) after a higher estrogen dose of approximately 30 micrograms/day for the next 30 days, respectively. Plasma aldosterone concentration was not affected by estrogen treatment. In contrast to CBG, binding of aldosterone to plasma aldosterone-binding globulin was totally absent before and following the estrogen treatment. The striking difference between the rabbit showing an absence of plasma protein binding of aldosterone and several other animal species is perhaps of great importance for the blood pressure regulation and for understanding of the particular resistance of blood pressure to salt or mineralocorticoids reported in this species.

Aldosterone↗
PubMed1987

Renin angiotensin aldosterone axis, including aldosterone binding globulin and blood pressure in three species of nonhuman primates.

Variables of renin-angiotensin-aldosterone axis with inclusion of protein binding to specific plasma globulin (ABG), plasma cortisol, and the blood pressure (BP) were measured in 24 chimpanzees, 4 gorillas, and 16 cynomolgus monkeys. ABG activity was readily detected in plasma from the primates. In chimpanzees and gorillas, all the variables under baseline conditions were similar to those in humans. In cynomolgus (Macaca fascicularis), both the ABG binding capacity for aldosterone and the diastolic or systolic BP were significantly higher (p less than 0.001 and p less than 0.01 respectively) than in chimpanzees and gorillas.

Aldosterone↗
PubMed1987

The relationship of plasma aldosterone-binding globulin to blood pressure regulation in young adults with cystic fibrosis.

Findings of increased secretion rate and decreased metabolic clearance rate (MCR) of aldosterone in patients with cystic fibrosis of the pancreas (CF) and our own evidence on the association of increased aldosterone-binding globulin (ABG)-binding and decreased MCR in essential hypertension (EH) inspired us to investigate the plasma aldosterone, with the inclusion of protein-binding variables, in CF patients. (1) The percentage of plasma aldosterone specifically bound to ABG was measured in 55 young adults with CF in addition to total plasma aldosterone, total plasma corticosteroids and for comparison of corticosteroid-binding globulin (CBG)-binding capacity. (2) The percentage of ABG-bound plasma aldosterone was found to vary with the seasonal change in temperature and the hepatic function of CF patients. Many of the CF patients, particularly during spring, summer and fall, had elevated plasma ABG-bound aldosterone which would be expected to result in low MCR. This binding was less elevated during cooler weather, suggesting that ABG-bound aldosterone is participating in the adaptation to warmer weather by probably increasing extrarenal sodium retention, thereby preventing a fall of blood pressure (BP) to pathologically low levels. A significant correlation was consequently found between the ABG capacity and the ambient temperature. (3) CF patients with low liver function had significantly lower protein binding of aldosterone and only slightly lower CGB capacity, presumably due to disturbed protein synthesis by the liver. (4) In some patients, elevated total plasma aldosterone and total corticosteroids were found, probably as a result of an adaptation to excessive sweat losses of sodium and the consequent contraction of intravascular volume. (5) Our findings also demonstrated a positive correlation between plasma ABG-bound aldosterone and both systolic and diastolic BP.

Adrenal Cortex Hormones↗
PubMed1986

Human salivary or plasma aldosterone- and dehydroepiandrosterone-binding glycoprotein induces hypertension in the rat.

In this study we demonstrated the presence of an aldosterone-binding globulin (ABG) in human saliva. Following ultrafiltration and purification of saliva to electrophoretic homogeneity, this thermolabile globulin called ABG-S appeared to be identical to plasma ABG. It was also shown that both purified ABG-S and plasma ABG bind reversibly, with high affinity (Ka = 1.6 X 10(-9) M, Scatchard plot) to dehydroepiandrosterone sulfate (DHEA-S) to binding sites different from those for aldosterone. Following incubation with human urine both ABG and ABG-S were converted quantitatively into corresponding thermostable forms which appeared to be identical with the human urinary ABG homologue namely ABG-TsU. In addition ABG-S showed the same ability to elevate blood pressure when administered to rats as did ABG-TsU. The fact that an endogenous substance with pressor activity might exist in more than one body fluid suggests further its possible participation in the basic mechanisms of blood pressure regulation.

Animals↗
PubMed1986

Association of decreased plasma cortisol and corticosteroid-binding globulin binding capacity in patients with essential hypertension and their first degree relatives.

Both plasma cortisol and total corticosteroid-binding globulin (CBG) binding capacity were lower in 210 patients with uncomplicated essential hypertension (EH) and their 66 hypertensive first degree relatives, compared with 171 controls. However, both variables were similar in 84 normotensive relatives to those found in control subjects showing extensive variation over the entire control-EH range. The association of reduced plasma cortisol and CBG binding capacity in EH may be closely related to altered steroid metabolism which may be partly explained by an abnormality mimicking a relative deficiency in adrenal 17 alpha- and 11 beta-hydroxylation. One manifestation of this disorder in EH is an increase in the secretion rate and plasma levels of dehydroepiandrosterone sulphate (DHEA-S) which is bound with high-affinity to a low-capacity specific plasma globulin and accounts for most of the digitalis-like activity of human plasma.

Adolescent↗
PubMed1985

Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians.

Yanomama Indians from the jungles of southern Venezuela and northern Brazil excreted 1 +/- 1.5 mEq of Na and 203 +/- 109 mEq of K and had low blood pressure (BP), 102/62 mm Hg). In comparison, Guaymi Indians of Panama excreted 103 +/- 50 mEq of Na and 118 +/- 52 mEq of K and had significantly higher BP (114/75 mm Hg, p less than 0.001). Elucidating the renin-aldosterone axis, total upright serum aldosterone in 34 Yanomama was high (85.6 +/- 78 ng/100 ml). The binding capacities of thermolabile (ABG) and thermostable (ABG-Ts) serum globulins for aldosterone were elevated at 23.8 +/- 6 and 14.9 +/- 2.6%, respectively; consequently, total ABG- plus ABG-Ts- bound aldosterone was as high as 38.6 +/- 6.3%. Plasma renin activity (PRA 10.3 +/- 2.4 ng/ml/h) and urinary aldosterone 18-glucuronide (70.3 +/- 30 micrograms/24 h) in 17 Yanomama were also very high. In contrast, total serum corticosteroids and corticosteroid-binding globulin (CBG) binding capacity were normal, suggesting normal ACTH activity. PRA correlated positively with total (r = 0.47, p less than 0.05) and free (r = 0.47, p less than 0.05) serum aldosterone, which in turn showed a negative trend with Na (r = 0.33, NS) excretion. The effect of high dietary K appeared less important to aldosterone stimulation and PRA suppression. ABG-bound aldosterone (r = 0.43, p less than 0.01) as well as ABG-Ts (r = 0.56, p less than 0.05) were negatively correlated with diastolic but not systolic BP. The total ABG- and ABG-Ts-bound fraction correlated with diastolic BP (r = 0.43, p less than 0.05) in contrast to the free fraction (r = 0.08, NS) or total aldosterone (r = -0.09). Apparently, only bound serum aldosterone is important for the maintenance of diastolic BP. High serum aldosterone, with elevated excretion, indicates an increased secretion rate; increased serum protein binding suggests an increased tissular activity and alterations in aldosterone metabolism. In Guaymi Indians both total plasma aldosterone (14.5 +/- 65 ng/100 ml) and urinary aldosterone (8.1 +/- 4.8 micrograms/creatinine excretion) were normal. ABG-binding capacity for aldosterone was moderately elevated (17.8 +/- 4.8) and of ABG-Ts normal (10.2 +/- 1.2) suggesting a nearly normal aldosterone metabolism and regulation. The BP of Guaymi was significantly higher than that of the Yanomama.

Adolescent↗
PubMed1985

Simple reproducible competitive radioligand assay for plasma protein binding of aldosterone.

A simple reliable and specific binding assay for the estimation of plasma (or serum) aldosterone-binding globulins (ABGs) is described. The method is based on the determination of the aldosterone-binding capacity of diluted plasma (with water 1:5), and relating it to the total aldosterone concentration in the same sample. The method distinguishes between the heat-labile and heat-stable ABG, the binding to the latter being determined following heating of plasma at 60 degrees C for 25 min. The binding to the heat-labile protein is determined by subtraction of the value for the binding to the heat-stable protein from the binding of the nonheated diluted plasma. Free aldosterone is separated from the bound fraction by adsorption of the former to dextran-coated charcoal. Two different concentrations of [3H]-aldosterone are used throughout the assay. Data obtained by incorporating chromatographic separation into the cross-reactivity procedure using several steroids are presented as evidence for the specificity of the method. This chromatography separates plasma ABG from corticosteroid-binding globulin. In 316 male or female controls, ABG capacity was 9.7 +/- 0.38% (SE)-range 2-17. Samples in females were taken during the first 8 days from the onset of menstruation. Higher ABG-binding capacity (p less than 0.001) was found during pregnancy.

Adolescent↗
PubMed1978

Role of the adrenal cortex and sodium in the pathogenesis of human hypertension.

After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described.

Adrenal Cortex↗
PubMed1978

Selective hypopituitarism with severe hyponatremia and secondary hyporeninism.

A female patient presenting clinically a severe hyponatremia was found to have a selective hypopituitarism with predominant ACTH and partial FSH, LH, and GH deficiency as well as a suppression of plasma renin activity and aldosterone. The adrenal cortex responded well in cortisol increase to ACTH infusion and in plasma aldosterone increase to angiotensin II infusion. The patient had pressor hyperreactivity to angiotensin II. The hyponatremia was caused by a negative sodium balance induced by excessive urinary loss which remained unaffected by mineralocorticoid treatment. Substitution doses of cortisol, however, corrected the disturbance with an increase in plasma renin activity and improvement in the sodium balance. The data are interpreted as indicating a direct or indirect regulatory (permissive?) effect of low doses of cortisol on plasma renin activity correcting the underlying disturbance--the secondary hyporeninism.

Adrenocorticotropic Hormone↗
PubMed1978

Increased aldosterone plasma protein binding in women on combined oral contraceptives throughout the menstrual cycle.

Plasma aldosterone concentration and the percentage of the fraction bound to a specific plasma aldosterone-binding globulin (ABG) were measured throughout the menstrual cycle in 26 healthy women aged between 19 and 38 yr who were receiving estrogen-containing oral contraceptives (OC), Midafternoon upright levels of total plasma aldosterone were similar in control and OC subjects and showed normal cyclic fluctuation in both groups. The percentage of ABG-bound aldosterone was markedly higher in OC subjects than in controls at all stages of the cycle and showed a positive correlation with the mean blood pressure when all OC subjects studied were considered. In addition, when the plasma ABG levels were measured 6 months or more after the start of medication, they appeared to be related to the dose of estrogen in the OC, but not to the length of time of its administration. The identity of plasma ABG in OC subjects with that in control subjects was also established.

Adult↗
PubMed1977

Effects of angiotensin II on steroid metabolism and hepatic blood flow in man.

Metabolic clearance rates (MCR) of aldosterone, cortisol, 11-deoxycorticosterone (DOC), corticosterone, and progesterone were simultaneously measured by constant infusion in eight control subjects before and during angiotensin II infusion in subpressor (3 ng/min per kg) and pressor (22 ng/min per kg) doses. Plasma levels of aldosterone and cortisol, the heat-labile protein-bound fraction of aldosterone, and hepatic blood flow (HBF) (as estimated by the fractional clearance of indocyanine green) were determined concomitantly. Angiotensin II in a subpressor dose produced a significant decrease of the MCR of aldosterone (by 23%), cortisol (by 16%), DOC (by 26%), corticosterone (by 14%) and progesterone (by 33%). The pressor dose further decreased the respective MCR by 37%, 21%, 40%, 28%, and 42% of the baseline value. Plasma aldosterone levels rose by 317% with subpressor and by 434% with pressor doses. HBF decreased by 18% with subpressor and by 33% with pressor doses of angiotensin II. Furthermore, there were significant negative correlations between the MCR of each steroid and the respective values of the fractional clearance of indocyanine green. We conclude that angiotensin II, by its vasoconstrictive action on the splanchnic vascular bed, decreases the MCR of aldosterone, cortisol, DOC, corticosterone, and progesterone. This decrease has to be taken into account when considering the stimulatory effect of angiotensin II on various plasma steroid concentrations.

Adrenal Cortex Hormones↗
PubMed1977

Response of several adrenal steroids to ACTH stimulation in essential hypertension.

Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F), and aldosterone were measured in 8 control subjects and in 10 patients with low and normal renin essential hypertension (EH) before and 4 and 8 h after an iv infusion of 25 units of ACTH. Secretion rates of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured for the 24 h prior to and the day of the ACTH infusions. The hypertensive patients had significantly higher plasma levels of aldosterone, DOC and S after ACTH than the controls, whereas plasma B levels were significantly lower. The low renin subgroup considered separately had significantly higher plasma levels of aldosterone and DOC than controls, and higher levels of B and lower levels of F than the normal renin subgroup in response to ACTH. Although not significantly different, the plasma levels of P and the secretion rate of 18-OH DOC tended to be higher, and plasma 17-OH P and F levels lower after ACTH in patients with EH than in controls. The low renin subgroup tended to have the highest plasma S levels and 18-OH DOC secretory rates and lowest F levels. Estimations of adrenal 11beta-hydroxylating efficiency in response to ACTH in patients and controls by plasma steroid ratios revealed significantly lower B/DOC ratios in both low and normal renin patients compared to controls, supported by somewhat lower F/S ratios in these patients, especially those in the low renin subgroup. Altered 17-hydroxylating efficiency seen by significantly lower 17-OH P/P ratios were also found in those with EH, supported by somewhat lower F/B and S/DOC ratios in these patients, agian especially in the low renin subgroup. These data are compatible with a pattern of altered adrenocortical steroid biosynthesis in essential hypertension bearing features similar to adrenal 11beta and 17alpha-hydroxylation deficiencies.

Adrenal Cortex Hormones↗