The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE, and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGEj and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytryptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing′s disease was stimulated by LH-RH, norepinephrine, glucagon and MEE but not by TRH. Plasma levels of ACTH, β-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE, and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing′s syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas.
SUMMARY 1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16–18 g/day) and after 7 days of a low salt intake (1–3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na + concentration: 147.7 ± 0.4 mmol/L vs 145.3 ± 0.5 mmol/L; P < 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt‐sensitive ( n = 8) and the non‐salt‐sensitive ( n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt‐sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt‐sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.
1. To test the influence of a sodium (Na+) stimulus within the central nervous system on the release of atrial natriuretic peptide (ANP), we examined the effects of intracerebroventricular infusion of high Na+ artificial cerebrospinal fluid (CSF) on blood pressure, urinary Na+ excretion and plasma ANP levels in conscious Wistar rats. 2. Infusion of high Na+ (0.6 mol/1) CSF into the lateral ventricle at a rate of 1 μl/min for 60 min significantly increased mean blood pressure and urinary Na+ excretion, while normal Na+ (0.15 mol/1) CSF had no effects. Plasma ANP levels were higher in the high Na+ CSF group than in the normal Na+ group (154 ±39 vs 52 ±19 pmol/l, P < 0.05). 3. Interruption of the sympathetic nervous system and the vascular action of vasopressin with intravenous hexamethonium and d(CH2)5Tyr(Me)arginine vasopressin attenuated the pressor and natriuretic responses to intracerebroventricular high Na+ CSF. Plasma ANP levels in these rats did not differ significantly from those in rats which were similarly treated but were given normal Na+ CSF. 4. These results indicate that elevation of the CSF Na+ concentration without peripheral volume loading can stimulate ANP release into the circulation. ANP release due to central Na+ stimulus appears to be mediated by the sympathetic nervous system, vasopressin, and/or haemodynamic change caused by these factors.
