Atrial natriuretic factor, catecholamines, and natriuresis.
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Animals↗
Biomedical subjects
K Racz
Publications and source records attributed to K Racz.
ANF-like peptide(s) in the peripheral autonomic nervous system.
The recent demonstration of the atrial natriuretic factor (ANF) within the brain has been extended in the present study by the additional localization of ANF-like activity in the peripheral nervous structures. Using a sensitive radioimmunoassay, it was possible to detect ANF-like immunoreactive peptide(s) in crude and chromatographically separated extracts of parasympathetic rat ganglia. The partially purified ANF-like peptide exhibited a biological action similar to cardiac ANF. This finding supports a possible involvement of ANF in the regulation of both, central and peripheral neuronal activities.
Adrenal Cortex↗
Sympathomedullary activity in one-kidney, one clip hypertensive rats.
In order to evaluate more directly the implications of the sympatho-adrenal system in one-kidney, one clip hypertension (1K1C), we studied adrenal catecholamine synthesis after a bolus injection of 3H-tyrosine, tissue norepinephrine and dopamine concentrations, as well as the urinary excretions of norepinephrine, epinephrine, dopamine and those of the major dopamine metabolites, dihydroxphenylacetic acid (DOPAC) and homovanillic acid (HVA) in 1K1C and control uninephrectomized rats. When compared with controls, the hypertensive rats had a markedly enhanced formation of adrenal 3H-norepinephrine and 3H-epinephrine, higher urinary norepinephrine and epinephrine excretions but lower heart and kidney content of norepinephrine and dopamine as well as decreased urinary excretions of the main dopamine metabolites, DOPAC and HVA. These data suggest an increased norepinephrine and epinephrine synthesis in 1K1C hypertensive rats associated with dopamine synthesis, which is normal but probably disproportionally low relative to the synthesis of norepinephrine and epinephrine. This abnormality may be an important pathogenetic factor in this model of experimental hypertension.
Adrenal Glands↗
Zona glomerulosa cell responses to atrial natriuretic factor in genetically hypertensive rats.
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.
Adrenocorticotropic Hormone↗
Atrial natriuretic factor inhibits the sympathetic nervous activity in one-kidney, one-clip hypertension in the rat.
The one-kidney, one-clip model of rat hypertension was found to have an increased natriuresis following chronic infusion of atrial natriuretic factor (ANF). We have now found that this natriuretic effect of ANF is associated with a suppression of the initially elevated urinary excretion of norepinephrine and epinephrine and increase of the excretion of the main dopamine metabolite-dihydroxyphenylacetic acid as well as of the urinary dopamine to norepinephrine ratio. These data are compatible with the hypothesis that ANF suppresses the increased sympathetic activity in this model of hypertension and this action combined with opposite changes of dopamine may contribute to the natriuretic effect of ANF.
Animals↗
The blood pressure decrease-induced sympathetic discharge following atrial natriuretic factor administration may offset its natriuretic action.
Conscious SHR and WKY rats were infused during 7 days with ANF (Arg 101-Tyr 126), 100 ng/hr/rat, by means of miniosmotic pumps and their basal blood pressure (BP), changes in sodium excretion and urinary catecholamines compared with those at the last day of the infusion. The SHR initial BP of 181 +/- 3 mmHg gradually declined to 137 +/- 5 mmHg. No significant change in blood pressure was observed in the ANF-infused WKY group. However, WKY rats exhibited an increased sodium excretion and urinary dopamine/norepinephrine ratio when compared to sham-infused rats. No such differences were observed in SHR. It is suggested that an ANF-induced withdrawal of the renal sympathetic tone permits the manifestation of its natriuretic action in WKY rats. When, however, a BP decrease predominates, as in SHR, this decrease results in a reflex sympathetic discharge with a renal sympathetic activity over-riding the ANF induced natriuresis seen in WKY rats. Secondary sympathetic responses to the ANF-induced BP decrease have to be thus taken into account when a dissociation between the hypotensive and natriuretic action of ANF is observed in vivo.
Animals↗
Role of sulfate conjugation of catecholamines in blood pressure regulation.
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.
Adrenal Cortex↗
Atrial natriuretic factor inhibits the early pathway of steroid biosynthesis in bovine adrenal cortex.
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.
Adrenal Cortex↗
ANF (Arg 101--Tyr 126) is the peptide secreted by rat atrial cardiocytes in culture.
The atrial natriuretic factor (ANF) secreted from rat cardiocytes in culture was purified and characterized. The purification procedure involves extraction of ANF by activated Vycor glass, followed by HPLC on C18 mu Bondapak and Vydac columns. The detection of ANF in column eluates was performed by a simple and sensitive radioimmunoassay. The amino acid composition and N-terminal amino acid sequencing appeared to be identical to the Arg 101 - Tyr 126 peptide. The isolated ANF showed biological activity, inhibiting basal and ACTH-stimulating aldosterone secretion from rat zona glomerulosa cells with the same potency as the synthetic peptide.
Adrenal Glands↗
In vivo release of adrenal catecholamines in rats by fusaric acid.
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.
Adrenal Glands↗
Peripheral dopamine synthesis and metabolism in spontaneously hypertensive rats.
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)
Adrenal Glands↗
Regional distribution of free and sulfoconjugated catecholamines in the bovine adrenal cortex and medulla.
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.
Adrenal Cortex↗
Direct beta-adrenergic stimulation of aldosterone secretion in cultured bovine adrenal subcapsular cells.
Primary culture of bovine adrenal subcapsular cells was used to investigate direct effects of catecholamines on aldosterone secretion. Cells dispersed with collagenase and DNAse and cultured at high density (1.5-2 million/ml) for 3 days displayed high sensitivity to angiotensin II and ACTH, with an ED50 of 1.4 and 1.5 nM, respectively. Adrenergic agonists elicited a 4- to 6-fold stimulation of aldosterone secretion with potency order (-)isoproterenol greater than (-)epinephrine equals (-)norepinephrine greater than (+)isoproterenol, and corresponding ED50 5, 240, 213, and 3000 nM, respectively. No reproducible inhibition by dopamine of basal or stimulated levels of aldosterone secretion could be detected, but a weak stimulatory effect was sometimes observed at high concentration greater than 10 microM. (-)Isoproterenol stimulation of aldosterone production was potently inhibited by the beta-adrenergic antagonists (-)alprenolol and (+)alprenolol with potencies of 1.8 and 110 nM, respectively. The alpha-adrenergic antagonists prazosin, yohimbine, and phentolamine only weakly inhibited (-)isoproterenol stimulation with potencies of 5, 13, and 140 microM, respectively. The potent beta 2-adrenergic antagonist ICI 118.551 and the weaker beta 1-adrenergic antagonist atenolol were roughly equipotent with potencies of 0.27 and 0.44 microM, respectively. Addition of the phosphodiesterase inhibitor Ro 20-1724 at 10 microM doubled the maximum stimulation effect of (-)isoproterenol without changing the potency of the catecholamine or the basal level of aldosterone secretion, suggesting a potential role of cAMP as a mediator of isoproterenol stimulation. These results indicate the presence of a beta 1-adrenergic receptor stimulating aldosterone secretion in bovine zona glomerulosa cells. The physiological significance of direct beta-adrenergic stimulation of aldosterone production is currently being assessed.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
Specific receptor-mediated inhibition by synthetic atrial natriuretic factor of hormone-stimulated steroidogenesis in cultured bovine adrenal cells.
The effect of synthetic atrial natriuretic factor (ANF) on adrenal steroidogenesis has been studied in primary culture of bovine adrenal cells. ANF-(8-33) produced a potent 40-70% inhibition of angiotensin II-, ACTH-, PGE1-, and forskolin-stimulated secretion of aldosterone production from zona glomerulosa cells with an ED50 of 120 pM. An equipotent inhibitory effect of the natriuretic factor on cortisol production was also observed in cultured zona fasciculata cells. Nicotine-stimulated secretion of catecholamines from medullary cells was only slightly inhibited by the factor at doses above 10 nM. [125I]iodo-ANF-(8-33) binding to glomerulosa membranes displayed an apparent affinity of 100-150 pM for specific receptor sites and was not inhibited by angiotensin II or ACTH. Conversely, the natriuretic factor had no affinity for angiotensin II receptor sites. The results demonstrate that part of the natriuretic effect of this new factor might be due to inhibition of adrenal steroidogenesis by action through a distinct receptor.
Adrenal Cortex↗
The adrenal synthesis and tissue content of dopamine increase when the blood pressure rises in spontaneously hypertensive rats.
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.
Adrenal Glands↗
An atrial natriuretic factor-like activity in rat posterior hypophysis.
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.
Adrenal Glands↗
Bromocriptine decreases blood pressure of spontaneously hypertensive rats without affecting the adrenomedullary synthesis of catecholamines.
Because of controversial data on the role of adrenomedullary catecholamines (CA) in the hypertension of spontaneously hypertensive rats (SHR) and in the hypotensive action of bromocriptine, we studied the effect of chronic bromocriptine treatment on blood pressure (BP), adrenal CA synthesis, tissue CA, and urinary excretions of CA and their metabolites in SHR. We found that the hypertension of 12-week-old SHR (systolic BP, 181 +/- 13 mm Hg) was reduced to 123 +/- 8 mm Hg when they received bromocriptine between 4 and 12 weeks of age (2 X 600 micrograms/kg/day, intraperitoneally). Although the urinary epinephrine (E) and the synthesis of adrenal norepinephrine (NE), E, and dopamine (DA), as well as the tissue content of CA in adrenals, heart, and kidney, remained unchanged after bromocriptine treatment, the urinary NE and DA excretions were lower in bromocriptine-treated SHR than in sham-treated SHR (NE, 2.7 +/- 0.3 versus 4.2 +/- 0.3 nmol/24 h in control SHR; DA, 18.7 +/- 1.6 versus 28.2 +/- 2.2 nmol/24 h in control SHR). In SHR, bromocriptine treatment did not affect the previously observed selectively increased adrenal turnover and synthesis of DA or the urinary excretions of normetanephrine (NM), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), or homovanillic acid (HVA). The results suggest that the bromocriptine-induced decrease of BP in SHR is not mediated by changes in adrenomedullary CA and that bromocriptine decreases the BP of SHR without affecting the previously observed increased adrenal DA release of SHR. Thus, other central or peripheral dopaminergic agonist actions of bromocriptine bypassing the adrenal medulla must be considered in the hypotensive action of the drug.
Adrenal Medulla↗