Effects of atrial natriuretic factor on cyclic GMP content in the rat aortic smooth muscle: studies on the role of membrane Na+,K+-ATPase.

1. These studies were conducted to determine whether preservation of the functional integrity of the membrane, Na+,K+-stimulated ATPase is essential for the atrial natriuretic factor (r-ANF-8-33) to enhance guanosine 3',5'-monophosphate (cGMP) content in the rat aortic smooth muscle. In freshly dissected rat aortic tissues, levels of cGMP were estimated using radioimmunoassay. 2. ANF (0.1 mumol/L in Krebs-Henseleit media) produced significant elevation in cGMP levels in the aortic smooth muscle when compared with that incubated in the control media, whereas suppression of Na+-pump with ouabain (1.0 mmol/L) and/or K+-free media did not produce any significant changes in the basal cGMP level; these two experimental manoeuvres did not prevent enhancement of cGMP by ANF. 3. Incubation of the tissues in the media containing ouabain plus vasoconstrictor concentrations of norepinephrine (0.3 mumol/L) also did not alter basal cGMP levels and did not prevent the ability of ANF to elevate cGMP. 4. These studies demonstrate that the antagonism by ouabain, of vasorelaxant effects of ANF (as reported in the literature) are not due to the prevention of the ability of ANF to enhance cGMP levels in the arterial smooth muscle. It is proposed that such an antagonism may be related to the actions of ouabain and ANF on diverse, and perhaps independent, mechanisms which affect Ca2+-fluxes across the cell membrane.

Dietary sodium intake and urinary dopamine and sodium excretion during the course of blood pressure development in Dahl salt-sensitive and salt-resistant rats.

Recent studies have suggested that dopamine (DA) formed within the kidney may play an important role in promoting sodium excretion, and that renal production and excretion of DA is determined by dietary sodium intake. Inasmuch as increased sodium consumption produces hypertension in Dahl salt-sensitive (DS) rats but not in Dahl salt-resistant (DR) rats, the present study was designed to examine the relationship between sodium consumption and urinary excretion of DA in these rats. DS and DR rats were placed on either high sodium chloride (8%) or low sodium chloride (0.4%) diets at 4 weeks of age and their systolic blood pressure (SBP), urine volume, urinary sodium and catecholamine excretion were measured once every week for the next 4 weeks. High sodium chloride diet increased SBP in DS rats at 6 weeks of age and SBP continued to rise until they were 8 weeks old. The SBP of DR rats did not reach hypertensive levels when they were given high sodium chloride diet. The SBP of DS rats on low sodium chloride diet was significantly higher than DR rats on the same diet. The urinary DA excretion increased with age in all four groups of rats and was similar when they were 8 weeks old. However, both DS and DR rats on high sodium chloride diet excreted greater amounts of sodium and had increased urine volume compared to the DS and DR rats on low sodium chloride diet. There were no significant differences in urinary NE or E excretion in these four groups of rats. Kidney levels of DA and NE were significantly lower in DS compared to DR rats on high sodium chloride diet. These results show that although there are no differences in urinary DA excretion between rats on low and high sodium intake, both DS and DR rats on high sodium chloride diet are able to exhibit a natriuretic response. The DS rats eliminate sodium at the expense of an elevated SBP whereas DR rats stay normotensive. Therefore, it appears that alterations in mechanisms controlling renal vascular resistance rather than sodium excretion are responsible for the development of hypertension in DS rats.

Opioid modulation of normal and pathological human chromaffin tissue.

To evaluate whether opioid receptor blockade might modulate sympathetic-adrenal activity, we studied the effects of placebo or naloxone administration on plasma catecholamine (CA) levels in a group of 13 normal subjects and 15 hypertensive patients suspected to have a pheochromocytoma. Diagnostic evaluation confirmed the presence of pheochromocytoma in 9 patients. Among these, 4 had a unilateral epinephrine (E)-secreting tumor, 3 had bilateral E-secreting tumors due to multiple endocrine adenomatosis type IIa, and 2 had a unilateral norepinephrine (NE)-secreting tumor. In each subject studied, CA secretion was evaluated by calculating the area (0-30 min) under the plasma hormone curves after placebo or naloxone administration. In normal subjects naloxone caused a significant increase (P less than 0.005) of E secretion, whereas NE did not change. Similarly, in the group of hypertensive patients, E secretion increased after naloxone (P less than 0.01). In pheochromocytoma patients naloxone caused a significant increase in E (P less than 0.05) and NE (P less than 0.01) secretion from E-producing tumors but no increase in the patients with NE-secreting pheochromocytomas. The study suggests that CA secretion from normal and pathological chromaffin tissue is modulated by endogenous opioids; this modulation seems particularly evident in patients with E-secreting pheochromocytoma.

Plasma catecholamine response to orthostasis in longstanding hypothyroidism.

In seven normotensive women affected by long-standing hypothyroidism norepinephrine peripheral levels were found significantly higher than after replacement therapy and than normal controls. After standing norepinephrine peripheral concentrations increased further; such an increase, although percentually lower than after therapy was sufficient to assure an adequate clinical response to orthostasis.