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We studied the effect of fusaric acid, an inhibitor of dopamine beta-hydroxylase (D beta H), on plasma and peripheral tissue catecholamine (CA) content and on urinary excretion of CA in the rat. We found that fusaric acid treatment resulted in a rapid decline of adrenal epinephrine (E) and norepinephrine (NE) and an increase of adrenal dopamine (DA); the kidney and heart NE and DA contents were affected in a pattern similar to that of the adrenals. In contrast, the E concentrations in the kidneys and heart were markedly elevated after a single intraperitoneal dose of fusaric acid (100 mg/kg); the maximum response was observed at 60 min, when kidney E increased from 9.3 +/- 4.4 to 101 +/- 24 pmol/g tissue and heart E in both atrium and ventricle rose from 92 +/- 8 to 607 +/- 85 pmol/g tissue and from 70 +/- 4 to 632 +/- 50 pmol/g tissue, respectively. In addition, a large increase of CA (predominantly of E) was found in the plasma of treated rats, where E, NE and DA were 27, 6.6 and 2.7 times higher than control values, respectively. The excretions of urinary E and NE were also significantly elevated during treatment. Fusaric acid-treated bilaterally adrenalectomized rats did not exhibit any increase in plasma, heart and kidney E concentrations. The results suggest that fusaric acid stimulates adrenal CA release in vivo, resulting in large increases of the main adrenal CA, E in peripheral tissues, plasma and urine. The decline in the adrenal E content is thus not only due to its decreased synthesis but also increased release.

We have studied several parameters of peripheral dopamine synthesis and metabolism in spontaneously hypertensive rats during the development of hypertension. Compared to Wistar-Kyoto rats, there was an increased dopamine content in 8-week-old spontaneously hypertensive rats in the adrenals (1.6 +/- 0.1 vs. 1.2 +/- 0.1 nmol/pair in Wistar-Kyoto rats) and kidneys (97 +/- 12 vs. 63 +/- 7 pmol/g tissue in Wistar-Kyoto rats), but the dopamine content in peripheral organs from normotensive 4-week-old spontaneously hypertensive rats did not differ from Wistar-Kyoto rats. In the heart, the dopamine increase was observed in 14-week-old spontaneously hypertensive rats (systolic blood pressure: spontaneously hypertensive rats, 189 +/- 9; Wistar-Kyoto rats, 106 +/- 2 mm Hg;) in both atrium (spontaneously hypertensive rats, 133 +/- 14; Wistar-Kyoto rats, 86 +/- 20 pmol/g tissue) and ventricle (spontaneously hypertensive rats, 41 +/- 6; Wistar-Kyoto rats, 23 +/- 5 pmol/g tissue). Urinary free dopamine and dihydroxyphenylacetic acid, but not norepinephrine or normetanephrine, in spontaneously hypertensive rats significantly increased between the ages of 7 and 11 weeks, reflecting the dopamine changes in tissue and suggesting a selective increase of the rate of dopamine synthesis and release.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined whether abnormalities in target cell responsiveness to atrial natriuretic factor (ANF), similar to those previously found in the kidney, could also be present in the zona glomerulosa cells of spontaneously hypertensive rats (SHR) and salt-sensitive Dahl rats (S rats). We found an attenuated aldosterone (Aldo) response to angiotensin II (ANG II) in zona glomerulosa cell suspensions isolated from hypertensive SHR compared with those from Wistar-Kyoto (WKY) rats, whereas cells derived from hypertensive S rats showed a significantly higher Aldo response to the maximum stimulatory dose of ANG II than those from salt-resistant Dahl rats (R rats). The maximum observed Aldo responses to ACTH stimulation were not different in SHR or S rats compared with their respective controls. ANF exerted a potent inhibitory action on both ANG II- and ACTH-stimulated secretions of glomerulosa cell suspensions, without any difference in its potency between hypertensive and control rats. The equipotent inhibitory action of ANF on the ANG II- and ACTH-stimulated secretion of Aldo in those cell suspensions suggests that the previously observed alterations in the target cell responsiveness to ANF do not exist in the adrenal zona glomerulosa cells of SHR and Dahl S rats.

We have previously determined that atrial natriuretic factor (ANF) is a potent inhibitor of steroid secretion in cultured bovine zona glomerulosa and fasciculata cells. The present report describes a comparison of the effect produced by ANF on aldosterone, deoxycorticosterone and progesterone secretions by zona glomerulosa cells and on cortisol, corticosterone and progesterone secretions by zona fasciculata cells. The equipotent inhibitory action of ANF on the stimulated secretion of these steroids in both cell types indicates a common site of action prior to progesterone synthesis at which ANF inhibits the steroidogenic pathway.

The presence of core antigens of retrovirus HTLV-III/LAV, referred to as "AIDS-related virus" (AV), has been sought in lymph node samples of patients with persistent generalized lymphadenopathy (PGL, 28 patients), prodromal AIDS (1 patient) and AIDS with Kaposi sarcoma (3 patients). In 30 patients the deposition of viral antigens, detected by monoclonal antibodies to HTLV-III and LAV, could be observed within the germinal centers (GCs) primarily within the extracellular network of immune complexes, and the two patients who were negative were atypical. No AV could be found in normal tonsil or in samples with follicular hyperplasia of unknown etiology (20 cases). These findings, taken together with the ultrastructural identification of typical retrovirus particles in all 9 PGL and 2 AIDS cases studied, indicates that the network of follicular dendritic (FD) cells is an important reservoir of AV virus antigen at this site. The persistence of this retrovirus inside the GCs helps explain how the follicular hyperplasia affecting FD cells and B blasts in PGL may in progressive cases be accompanied by destruction of FD cells and gradual development of T4+ lymphopenia. T4+ T cells may circulate through the GCs and become infected with AV there. In addition, the identification of retrovirus antigen in situ may be of diagnostic value.

The intraadrenal distribution of free and sulfoconjugated catecholamines and the activity of the catecholamine sulfoconjugating enzyme phenolsulfotransferase in the bovine adrenal gland are described. In the adrenal cortex all three free catecholamines, epinephrine, norepinephrine, and dopamine, were detected in various concentrations. In the adrenal medulla, the relative proportion of the main adrenal catecholamines, free epinephrine and free norepinephrine, was found to be higher in the medullary sections derived from the subcortical areas where the ratio of epinephrine to norepinephrine was 8:1 than in the centre of the organ where norepinephrine levels reached those of epinephrine. Free dopamine, representing about 1.0% of the total catecholamine content was distributed in the same pattern as epinephrine or the sum of epinephrine and norepinephrine, revealing a significant positive correlation between regional dopamine and epinephrine plus norepinephrine (r = 0.97) as well as between dopamine and epinephrine (r = 0.96). Phenolsulfotransferase activity was present in both medulla and cortex. Dopamine sulfate was detected in relatively small concentration in all cortical and medullary layers, but norepinephrine sulfate and epinephrine sulfate were not present. The meaning of this distribution of individual catecholamines and phenolsulfotransferase activity in both cortex and medulla is discussed.

Catecholamine sulfates were found to be inactive at vascular receptor sites. Only at one nonvascular receptor site important for blood pressure (BP) regulation was dopamine-3-O-sulfate found to be an inhibitory modulator of the adrenocortical secretion of aldosterone in vitro. However, sulfation of catecholamines (CA) does play an important role in BP regulation, as shown by the following observations: Sulfoconjugated CA with a long half-life are sometimes better markers of CA release than free CA, which have short half-lives. This is particularly true of dopamine (DA) sulfate because free DA, being rapidly sulfoconjugated, is usually undetectable. This led to the recognition of a previously unsuspected role of DA in paroxysmal hypertension and orthostatic hypotension. Measurements of CA sulfates reveal potentially important storage functions for sulfoconjugation that can rapidly inactivate excessive circulating free CA and so mitigate their cardiovascular impact while building up a pool of conjugated CA. The possibility that free CA can be generated from this pool through deconjugation whenever a need for them arises should be further investigated. Reproducible individual differences in the velocity of the sulfoconjugation of infused free CA can be detected, which suggests a genetic control of certain components of the sulfoconjugating process. These differences in sulfoconjugation probably modulate the cardiovascular action of CA and of some drugs with similar structure that also undergo sulfoconjugation.

The purpose of this study was to evaluate the body fluid and hormonal responses to salt loading in patients with idiopathic edema. In response to a combined intravenous and oral salt loading, patients with idiopathic edema were found, compared to control women, to have more weight gain, an increase in systolic and diastolic blood pressure, lower excretion of sodium and free dopamine (both the latter being partially accounted for by a diminished salt loading-induced increase in the creatinine clearance), and less plasma dopamine-beta-hydroxylase suppression. There were, between the groups, no differences in plasma and urinary concentrations of the dopamine precursor (dihydroxyphenylalanine), metabolites (dihydroxyphenyl-acetic and homovanillic acid, methoxytyramine and dopamine sulfate), or suppressibility of hormones which are under a partial dopaminergic inhibitory control (plasma renin activity, aldosterone and norepinephrine) by high salt. The inappropriate sodium retention, weight gain, and blood pressure increase following salt loading in idiopathic edema is thus associated with a blunted increase in the glomerular filtration and urinary dopamine excretion rates, as well as plasma dopamine-beta-hydroxylase non-suppressibility by saline. Some circumstantial evidence suggests that the dopamine deficiency is part of a wider disturbance within the cascade of natriuretic hormones.

An atrial natriuretic factor-(ANF) like immunoreactivity (IR-ANF), is present in the posterior hypophysis of the rat. In order to obtain more direct information on the presence and biological activity of this new posterior hypophysis peptide, we applied a procedure similar to that described for rat atria, to extract an ANF-like material from the posterior hypophysis of the rat. An analysis of the tissue extracts by reverse-phase high performance liquid chromatography (RP-HPLC) suggested that, in this organ, the ANF-like peptides may be present in multiple forms: a low molecular weight peptide which had a RP-HPLC pattern similar to that of the synthetic rat 28 amino acid C-terminal (Ser 99-Tyr 126) ANF, and an unidentified higher molecular weight peptide. The partially purified low molecular weight peptide was found to have a potency similar to that of synthetic rat ANF in the inhibition of adrenocorticotropin-stimulated aldosterone secretion in dispersed zona glomerulosa cells, suggesting that the ANF-like peptide was biologically active. Immunohistochemical visualization of the ANF-like peptides revealed the distribution of the peptide within the posterior hypophysis. There was no immunohistochemical staining for ANF in the intermediate lobe. These results suggest the existence of biologically active ANF-like peptides within the posterior hypophysis of the rat. It is possible that these peptides may modulate locally the posterior hypophysis hormone secretion.

Hypertensive (eight-week-old) but not normotensive (four-week-old) spontaneously hypertensive rats (SHR) have a higher adrenal dopamine (DA) synthesis and release, DA concentration in adrenals and kidney and urinary excretion of DA, dihydroxyphenylacetic acid and methoxytyramine than control WKY rats. At age 14 weeks, with progressive hypertension, the heart atria and ventricle DA content also increases. These abnormalities remain unaccompanied by changes in norepinephrine and epinephrine. Increased DA release, tissue content and urinary excretion of DA and its metabolites are thus selectively involved in the sequence of events leading to hypertension in SHR.