Cloned rat parathyroid cells (PTr cell line) that produce parathyroid hormone-related peptide plus endothelin 1 and primary cultures of human parathyroid cells were tested for growth and ...differentiation responses to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). High- and low-affinity binding sites for ANP were found on PTr cells; BNP appeared to bind to the same receptors with similar affinities. Either ANP or BNP stimulated production of cGMP and caused a 30% decrease in Na+-K+-Cl-cotransport. Each peptide increased synthesis and secretion of endothelin 1 by PTr cells in a dose-dependent fashion, but cell growth was not affected. Human parathyroid cells (normal and pathological) also responded to ANP or BNP with an increase in cGMP production. The finding of receptors for natriuretic hormones on parathyroid cells with consequent effects on release of endothelin 1 might be of relevance in understanding the clinical association between hyperparathyroidism and hypertension.
We studied the effects of presynaptic dopamine (DA) 2 receptor blockade on the sympathetic-adrenal response to graded exercise in seven normal men. DA2 receptor blockade was achieved by means of ...domperidone (DMP) administration. The exercise consisted of progressive cycling activity, from 30-80% of the predetermined maximal oxygen consumption for each man. Systolic, diastolic, and mean arterial pressures; heart rate; and plasma norepinephrine (NE), epinephrine (E), PRL, glucose, lactate, FFA, sodium, potassium, cortisol, and PRA were measured at rest, during exercise, and during recovery after placebo or DMP administration. Graded exercise caused significant increases in systolic and mean arterial pressures and plasma NE, E, lactate, sodium, potassium, FFA, cortisol, and PRA. DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations. These results strongly suggest that endogenous DA limits catecholamine release during sympathetic-adrenal stimulation by activating DA2 receptors.
To determine the appropriate choice of imaging techniques for localization of nodular lesions of parathyroid glands.
First, computed tomographic (CT), magnetic resonance (MR), ultrasonographic (US), ...and technetium 99m methoxyisobutyl-isonitrile (MIBI) scintigraphic images in 49 patients with primary hyperparathyroidism were retrospectively evaluated. A single-blind, prospective study that included 16 patients with primary hyperparathyroidism was then conducted. MR, US, scintigraphic, and color Doppler US images of the neck were obtained and analyzed.
In the retrospective study, CT, MR imaging, and US had low sensitivity (13%, 17%, and 27%, respectively) and specificity (39%, 65%, and 65%, respectively). Scintigraphy had 57% sensitivity and 85% specificity. In the prospective study, the use of latest-generation MR and US equipment and the participation of experienced operators led to improved sensitivity and specificity for these techniques. The combination of US and scintigraphy resulted in improved sensitivity (96%), specificity (83%), and positive and negative predictive values (88% and 94%, respectively), relative to the results obtained with either method alone. Doppler US was of little help in the setting of small glands.
The combination of (99m)Tc MIBI scintigraphy and US performed by well-trained operators with up-to-date instruments appeared to be the best diagnostic tool for the preoperative diagnosis of parathyroid disease.
125IAtrial natriuretic peptide (ANP) was used to identify ANP receptors on a clonal line of bovine bone endothelial (BBE) cells. Specific binding of 125IANP was saturable and of high affinity. ...Computer analysis of the equilibrium binding data indicated that the Scatchard plots are best fit by a straight line (Kd = 69.3 +/- 20.9 pM; binding capacity = 37.9 fmol/10(6) cells). The order of potency for competing with 125IANP binding was human ANP (hANP) > rat atriopeptin-1 (rAP-1) > porcine brain natriuretic peptide (pBNP) > porcine C-type natriuretic peptide. Affinity cross-linking studies indicated the presence of two major 130- and 70-kilodalton bands that specifically bound to hANP, rAP-1, pBNP, and porcine C-type natriuretic peptide. The binding of natriuretic peptides to BBE cells resulted in an increase in cGMP production and a significant decrease in Na+/K+/Cl- cotransport, without effects on cAMP intracellular accumulation. hANP, rAP-1, and pBNP at 100-nM concentrations, significantly inhibited PTH-induced cAMP production. Treatment with natriuretic hormones was also associated with an increase in 6-keto-prostaglandin F1 alpha levels in the culture medium of BBE cells and a higher cell growth rate. These studies demonstrate that bone endothelial cells bear receptors for natriuretic hormones associated with changes in PTH-induced cAMP production, prostaglandin production, and cell proliferation.
Plasma levels of brain natriuretic peptide, a recently identified cardiac hormone with natriuretic activity, were measured in 11 healthy subjects, 13 cirrhotic patients without ascites, 18 ...nonazotemic cirrhotic patients with ascites and 6 patients with cirrhosis, ascites and functional kidney failure. Plasma levels of brain natriuretic peptide were similar in healthy subjects and cirrhotic patients without ascites (5.56 ± 0.65 and 7.66 ± 0.68 fmol/ml, respectively). In contrast, cirrhotic patients with ascites, with and without functional kidney failure, had significantly higher plasma concentrations of brain natriuretic peptide (19.56 ± 1.37 and 16.00 ± 1.91 fmol/ml, respectively) than did healthy subjects and patients without ascites (p < 0.01); no significant difference was found between the two groups of cirrhotic patients with ascites with respect to this parameter. In the whole group of cirrhotic patients included in the study, brain natriuretic peptide level was directly correlated with the degree of impairment of liver and kidney function, plasma renin activity and plasma levels of aldosterone and atrial natriuretic peptide. The results of this study indicate that brain natriuretic peptide is increased in cirrhotic patients with ascites and suggest that sodium retention in cirrhosis is not due to deficiency of this novel cardiac hormone. (HEPATOLOGY 1992;16:156–161.)
Preliminary hormonal studies in a 18-y old man with the clinical features of Cushing's syndrome showed inconclusive and conflicting results both in basal conditions and after metyrapone and ...dexamethasone administration. Therefore the possibility of a cyclical or acyclical fluctuation of adrenal hypersecretion was suspected and the patient was observed for an extended period of time free of hormonal manipulations. Regular cycles of cortisol hyperproduction, with peaks occurring every 6.0 days were found. Ectopic ACTH production was ruled out and, even in the absence of radiological evidence of a pituitary adenoma, conventional cobaltotherapy was suggested after refusal of transsphenoidal pituitary surgery. About 8 months later a marked clinical improvement was evident as well as normalization of hormonal data with loss of the cyclical pattern. Remission of the disease was still persistent 15 and 28 months later. A recent control, approximately 4 1/2 yr after treatment confirmed the normalization of biochemical data, suggesting a cure of the disease.
Naloxone administration has no effect on plasma gonadotropin levels of agonadal men. The present study was designed to evaluate whether testosterone replacement therapy could restore LH ...responsiveness to naloxone in such men. We measured plasma LH and FSH levels at 15-min intervals during naloxone infusion (8 mg in 1 min followed by 12 mg in 3 h) and for the following 3 h in a group of agonadal men both before and after at least 2 months of three different schedules of testosterone replacement therapy: 1) testosterone undecanoate, 40 mg three times a day by mouth; 2) testosterone enanthate 200 mg im every 2 weeks; and 3) testosterone enanthate 100 mg im once a week. Mean plasma gonadotropin levels as well as LH pulse frequency did not vary during naloxone infusion vs. placebo either basally or during each testosterone regimen. These results suggest that long term testosterone therapy does not affect the altered opioid modulation of gonadotropin secretion which is present in agonadal men.
We assessed the cardiovascular and renal effects of human brain natriuretic peptide (BNP) infused at a dose inducing an increase in plasma BNP to pathophysiologic levels, in eight hypertensive ...patients in a randomized, placebo-controlled, crossover study. Left ventricular performance, cardiac output (echocardiography), heart rate, arterial pressure, glomerular filtration rate (GFR; creatinine clearance), sodium excretion, intrarenal sodium handling (lithium clearance method), and urine flow rate were measured in the infusion and postinfusion periods (1 h each), together with plasma BNP and the urinary excretion rate of cGMP. Plasma BNP levels increased from 2.90 ± 0.74 to 36.43 ± 5.51 pmol/L (
P < .01) at the end of the infusion and were still elevated at the end of the postinfusion period (7.03 ± 1.41 pmol/L,
P < .05). The urinary excretion of cGMP was also significantly higher during BNP infusion. Left ventricular performance, cardiac output, arterial pressure, and peripheral vascular resistance were not affected by BNP. Peptide infusion induced a significant increase in GFR (placebo, 115 ± 24; BNP, 147 ± 19 mL/min), sodium excretion (placebo, 129 ± 40; BNP, 243 ± 60 μmol/min), and urine flow rate. All these effects were observed also in the postinfusion period. The natriuretic effect of BNP was attributable to both an increase in filtered sodium load and a reduction of distal sodium reabsorption. These results suggest that BNP may contribute to maintain renal function and sodium excretion in patients with essential hypertension.
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