Effects of fasting on aldosterone secretion in ovariectomized rats.

The present study was designed to assess the effect of fasting on aldosterone secretion in ovariectomized (Ovx) rats. Ovx rats were divided into fed (allowed access to food ad libitum) and fasted (deprived of food for 24 hours) groups. The trunk blood of fed and fasted rats was collected after decapitation. In the in vitro study, adrenal zona glomerulosa (ZG) cells from fed or fasted rats were incubated with angiotensin II (Ang II, 10(-6) M), adrenocorticotropic hormone (ACTH, 10(-9) M), or forskolin (an activator of adenylyl cyclase, 10(-6) M) at 37 degrees C for 30 min. The levels of aldosterone in medium and plasma extracts were measured by radioimmunoassay. Results showed that the levels of plasma aldosterone in fasted rats were lower than those in fed rats. There were no significant differences in basal and Ang II-stimulated aldosterone secretion between fed and fasted groups. The increment of aldosterone induced by ACTH in fasted group was significantly less than that in fed group. Administration of forskolin led to a significant increase in aldosterone secretion in both fed and fasted groups. Fasted group had a decreased aldosterone secretion in response to forskolin as compared with fed group. In summary, these results suggest that fasting decreases aldosterone secretion in Ovx rats through a mechanism in part involving a reduction of aldosterone production in response to ACTH, a decreased activity of adenylyl cyclase, and/or an inhibition of post-cAMP pathway in ZG cells.

Aging effects on the secretion of corticosterone in male rats.

BACKGROUND: The effects of aging on zona fasciculatareticularis (ZFR) cell function in male rats were studied. METHODS: Male rats 3, 6, and 22 months of age were divided into three groups, and collagenase-dispersed ZFR cells were isolated and incubated with adrenocorticotropin (ACTH), 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), ovine prolactin (oPRL), deoxycorticosterone (DOC), or 3-isobutyl-l-methylxanthine (IBMX) at 37 degrees C for 1 hour. Corticosterone concentrations in cell media and cAMP production in ZFR cells were measured by radioimmunoassay. Protein expression of PRL receptor in ZFR cells were analyzed by Western blot. RESULTS: The basal levels of plasma and medium corticosterone were higher in 22-month-old than in 3-month-old rats. In contrast, the release of corticosterone in response to ACTH, 8-Br-cAMP, and DOC was lower in 22-month-old than in 3- and 6-month-old rats. Aging decreased the oPRL-stimulated release of corticosterone but increased the protein expression of PRL receptor in ZFR cells. The basal levels of intracellular cAMP increased with age. However, the ACTH-stimulated production of intracellular cAMP decreased in 22-month-old compared with 3- or 6-month-old rats. The increment of cAMP accumulation in ZFR cells after administration of IBMX was greater in 22-month-old than in 3- or 6-month-old rats. CONCLUSIONS: These results suggest that the aging effects on the production of corticosterone in rat ZFR cells is associated with change of the generation of cAMP, the activity of 11 beta-hydroxylase and the protein expression of PRL receptor.

Effects of thyroid hormones on the release of calcitonin gene-related peptide (CGRP) by rat prostate glands in vitro.

It has been well known that calcitonin (CT) and calcitonin gene-related peptide (CGRP) are derived from the CT/CGRP gene which is localized in chromosome 11. CGRP is a 37-amino acid neuropeptide expressed predominantly in the nervous system and is one of the most potent endogenous vasodilatory peptides that have been found. Only few reports described the distribution of CGRP in reproductive organs. Moreover, the hormonal regulation of CGRP secretion is still not clear. The present study was designed to examine the presence of CGRP in rat prostates and the direct effect of thyroxine (T4) on the release of CGRP by rat prostate glands in vitro. Male rats were thyroidectomized (Tx) or sham Tx for two weeks before decapitation. The ventral prostate glands were either extracted by phosphate buffer saline or bisected and preincubated with Locke's solution containing 10 mM glucose, 0.03% bacitracin, and 0.05% Hepes at 37 degrees C for 90 min. The hemi-prostate tissues were then incubated with Locke's medium containing T4 (0 to approximately 10(-7) M) for 1 hr. After incubation, the medium was collected, and the prostate tissues were weighed. The concentration of CGRP in both medium and prostate tissue extracts were measured by a specific radioimmunoassay (RIA) developed in our laboratory. Incubation of T4 at 10(-9) M was effective to increase the release of CGRP in rat prostate glands. Incubation of rat prostate glands with T4 at 10(-7) M resulted in a maximal release of CGRP (270% of the basal). These results suggest that thyroid hormones increase CGRP release by acting directly on rat prostate glands.

Age-related impairment of aldosterone secretion in zona glomerulosa cells of ovariectomized rats.

BACKGROUND: Clinical reports have revealed impaired sodium and water balance in elderly persons. The present studies were designed to investigate the effects and involved mechanisms of aging on aldosterone secretion in zona glomerulosa (ZG) cells of young and old ovariectomized (Ovx) rats. METHODS: Young (3 months) and old (24 months) female rats were Ovx for 4 days before decapitation. ZG cells of young and old rats were incubated with angiotensin II (Ang II), tetrandrine, nifedipine, adrenocorticotropic hormone (ACTH), forskolin, 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP), and precursors at 37 degrees C for 30 minutes. Aldosterone concentrations in plasma and cell media as well as 3':5'-cAMP production in ZG cells were determined by radioimmunoassay. The effects of aging on the activity of aldosterone synthase and the expression of cytochrome P450 side-chain cleavage enzyme (P450scc) in ZG cells were determined by thin-layer chromatography and Western blot analysis, respectively. RESULTS: Old rats had a lower plasma aldosterone level and a reduced basal aldosterone release from ZG cells than those in young rats. The conversions of steroidogenic precursors to aldosterone and the activity of aldosterone synthase as well as the expression of P450scc in ZG cells were lower in the old group than in the young group. Ang II-, ACTH-, forskolin- or 8-Br-cAMP-stimulated aldosterone secretion was attenuated in the old group as compared with the young group. Nifedipine decreased aldosterone secretion in the young group but not in the old group. The basal and forskolin-stimulated cAMP accumulations were lower in the old than in the young group. CONCLUSIONS: These results suggest that the age-related decline in aldosterone secretion is in part a consequence of the reduced activities of biosynthetic enzymes, adenylyl cyclase and L-type calcium channels, as well as the expression of P450scc protein in ZG cells.

Inhibition of aldosterone production by testosterone in male rats.

In vivo and in vitro experiments were designed to assess the effect of testosterone on aldosterone secretion in male rats. Orchidectomized rats were injected subcutaneously with oil or testosterone propionate ([TP] 2 mg/kg) for 7 days. Intact rats were injected with oil only. The results indicate that the plasma aldosterone level was higher in orchidectomized versus intact and TP-replaced rats. In the in vitro study, testosterone caused a marked decrease of aldosterone secretion by zona glomerulosa (ZG) cells, but failed to alter the accumulation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Testosterone significantly decreased the corticotropin (ACTH)-stimulated production of aldosterone and accumulation of cAMP in rat ZG cells. The conversion of corticosterone to aldosterone and of 25-OH-cholesterol to pregnenolone, as well as angiotensin II (ANG II)-stimulated production of aldosterone, were decreased by testosterone. These results suggest that testosterone inhibits the basal and ANG II- and ACTH-stimulated release of aldosterone, via inhibition of aldosterone synthase activity and cytochrome P-450 side-chain cleavage (P450scc) activity, and ACTH-stimulated cAMP accumulation in rat ZG cells.

Age-related differences in corticosterone secretion in female rats.

The effects of age on steroidogenesis in rat zona fasciculata-reticularis (ZFR) cells were studied. Young, adult, and middle-aged rats were ovariectomized (Ovx) and received replacement therapy with oil or estradiol benzoate ([EB] 25 microg/mL/kg). Rat ZFR cells were incubated with corticotropin (ACTH), prolactin (PRL), or forskolin at 37 degrees C for 1 hour. The effects of age on the activity of steroidogenic enzymes of ZFR cells were measured by the amount of intermediate steroidal products separated by thin-layer chromatography. Plasma levels were higher for PRL (54% to 254%) and corticosterone (179% to 257%) in middle-aged versus young rats. In oil-treated Ovx rats, basal and ACTH-stimulated corticosterone release by ZFR cells were also greater in middle-aged compared with young rats. Replacement with EB in Ovx rats increased the ACTH-stimulated release of corticosterone. Administration of ovine PRL in vitro resulted in a dose-dependent increase of corticosterone production. In oil-treated middle-aged rats, ovine PRL-stimulated corticosterone release was higher than in young rats. Forskolin-induced production of cyclic adenosine 3',5'-monophosphate (cAMP) was greater in middle-aged versus young rats and correlated with the increase of corticosterone production. The activity of steroidogenic enzymes in rat ZFR cells was unchanged by age. These results suggest that the age-related increase of corticosterone production in female rats is associated with the stimulatory effect of PRL on ZFR cells and is due in part to an increase of cAMP generation.

Effects of estradiol on aldosterone secretion in ovariectomized rats.

The effects and action mechanisms of estradiol on aldosterone secretion in female rats were studied. Replacement of estradiol benzoate (EB) increased the levels of plasma estradiol and aldosterone in ovariectomized (Ovx) rats. The aldosterone release from zona glomerulosa (ZG) cells was higher in EB-treated rats than in oil-treated animals. EB treatment potentiated the responses of aldosterone release to adrenocorticotropic hormone (ACTH), forskolin (FSK), and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Administration of EB in vivo did not alter cAMP production in response to ACTH or FSK. Although angiotensin II (Ang II) increased aldosterone secretion by rat ZG cells, the stimulatory effect of Ang II on the release of aldosterone was not altered by EB treatment. The conversions of [3H]-deoxycorticosterone to [3H]-corticosterone and [3H]-corticosterone to [3H]-aldosterone in EB-treated groups were greater than those in the oil-treated group. These results suggest that estradiol increases aldosterone secretion in part through the mechanisms involving the activation of the post-cAMP pathway, 11beta-hydroxylase and aldosterone synthase activity.

Effects of prolactin on aldosterone secretion in rat zona glomerulosa cells.

Acute effects and action mechanisms of prolactin (PRL) on aldosterone secretion in zona glomerulosa (ZG) cells were investigated in ovariectomized rats. Administration of ovine PRL (oPRL) increased aldosterone secretion in a dose-dependent manner. Incubation of [3H]-pregnenolone combined with oPRL increased the production of [3H]-aldosterone and [3H]-deoxycorticosterone but decreased the accumulation of [3H]-corticosterone. Administration of oPRL produced a marked increase of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in ZG cells. The stimulatory effect of oPRL on aldosterone secretion was attenuated by the administration of angiotensin II (Ang II) and high potassium. The Ca2+ chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA, 10(-2) M), inhibited the basal release of aldosterone and completely suppressed the stimulatory effects of oPRL on aldosterone secretion. The stimulatory effects of oPRL on aldosterone secretion were attenuated by the administration of nifedipine (L-type Ca2+ channel blocker) and tetrandrine (T-type Ca2+ channel blocker). These data suggest that the increase of aldosterone secretion by oPRL is in part due to (1) the increase of cAMP production, (2) the activation of both L- and T-type Ca2+ channels, and (3) the activation of 21-hydroxylase and aldosterone synthase in rat ZG cells.

Direct effects of prolactin on corticosterone release by zona fasciculata-reticularis cells from male rats.

The role of prolactin (PRL) in the male is not fully defined. The aim of this study was to investigate the function and mechanism of PRL on the production of corticosterone by zona fasciculata-reticularis (ZFR) cells in vitro. The ZFR cells were obtained from male rats under normal, hyperprolactinemic, or hypoprolactinemic situation. PRL stimulated the corticosterone release in a dose-dependent pattern in the ZFR cells from normal male rats. The cellular adenosine 3'-5'-cyclic monophosphate (cAMP) concentration positively correlated with PRL concentration in the presence of forskolin or 3-isobutyl-1-methylxanthine (IBMX). PRL enhanced the stimulatory effects of cAMP mimetic reagents, i.e., forskolin, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), and IBMX on the release of corticosterone. The adenylate cyclase inhibitor (SQ22536) inhibited the corticosterone release in spite of presence of PRL. Nifedipine (L-type calcium channel blocker) did not inhibit corticosterone release. The hyperprolactinemic condition was actualized by transplantation of donor rat anterior pituitary glands (APs) under kidney capsule. By comparison with the cerebral cortex (CX)-grafted group, AP-graft resulted in an increased release of corticosterone, 3beta-hydroxysteriod dehydrogenase (HSD) activity and cAMP production by ZFR cells. Acute hypoprolactinemic status was induced by bromocriptine for 2 days. The results showed the productions of corticosterone were lower in hypoprolactinemic group than in control group, which were persistent along with different ACTH concentrations. These results suggest that PRL increase the release of corticosterone by ZFR cells via cAMP cascades and 3beta-HSD activity.

Pharmacological effects of propylthiouracil on corticosterone secretion in male rats.

BACKGROUND: We investigated the direct effects of propylthiouracil (PTU) on corticosterone secretion both in vivo and in vitro. METHODS: Male rats were divided into 4 groups and then injected subcutaneously with saline, PTU, PTU plus thyroxine (T4), or T4 once daily for 2 weeks. After 2 weeks, rats were decapitated or received adrenocorticotropic hormone (ACTH), intravenously. Zona fasciculata-reticularis (ZFR) cells from normal, saline-, PTU-, PTU plus T4-, or T4-treated rats were incubated with ACTH, forskolin, 8-Br-cAMP, deoxycorticosterone (DOC) +/- PTU (1, 2, or 5 mg/mL) at 37 degrees C for 2 hours. Corticosterone concentrations in plasma and cell media, and 3':5'-cyclic adenosine monophosphate (cAMP) production in ZFR cells were determined by radioimmunoassay. The effects of PTU on the activities of steroidogenic enzymes in ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. RESULTS: The basal and ACTH-stimulated levels of plasma corticosterone in PTU-treated rats were lower as compared to saline-treated animals. Both basal and ACTH-stimulated corticosterone secretion were inhibited by PTU > 2 mg/mL in rat ZFR cells. The cAMP production induced by forskolin was lower in PTU, PTU plus T4, or T4-treated rats than in saline-treated animals. Chronic administration of PTU or PTU plus T4 inhibited the 3 beta-hydroxysteroid dehydrogenase, 21 beta-hydroxylase, and 11 beta-hydroxylase activities. Administration of PTU (1, 2, and 5 mg/mL) suppressed the basal, ACTH, 8-Br-cAMP, forskolin, and DOC-stimulated corticosterone secretion in rat ZFR cells. Likewise, PTU > 2 mg/mL inhibited the ACTH and 8-Br-cAMP-stimulated levels of intracellular cAMP in rat ZFR cells. CONCLUSIONS: These results suggest that PTU counteracts both basal and ACTH-induced adrenal steroidogenesis through their attenuation of the activity of 11 beta-hydroxylase and cAMP production in rat ZFR cells.

Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats.

1. The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. 2. Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine. 3. Plasma CCK levels were increased dose-dependently by amphetamine. 4. Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inhibition of gastric emptying and the decrease in GI transit in male rats. 5. The selective CCK(A) receptor antagonist, lorglumide, dose-dependently attenuated the amphetamine-induced inhibition of gastric emptying in male rats. In contrast, the selective CCK(B) receptor antagonist, PD 135,158, did not reverse the effect of amphetamine on gastric emptying. 6. Both lorglumide and PD 135,158 reversed the inhibitory effect of amphetamine on GI transit in male rats. 7. These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.

Acute effects of thyroid hormones on the production of adrenal cAMP and corticosterone in male rats.

The acute effects of thyroid hormones on glucocorticoid secretion were studied. Venous blood samples were collected from male rats after they received intravenous 3,5,3'-triiodothyronine (T3) or thyroxine (T4). Zona fasciculata-reticularis (ZFR) cells were treated with adrenocorticotropic hormone (ACTH), T3, T4, ACTH plus T3, or ACTH plus T4 at 37 degrees C for 2 h. Corticosterone concentrations in plasma and cell media, and also adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells in the presence of 3-isobutyl-1-methylxanthine, were determined. The effects of thyroid hormones on the activities of steroidogenic enzymes of ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Administration of T3 and T4 suppressed the basal and the ACTH-stimulated levels of plasma corticosterone. In ZFR cells, both thyroid hormones inhibited ACTH-stimulated corticosterone secretion, but the basal corticosterone was inhibited only with T3 > 10(-10) M or T4 > 10(-8) M. Likewise, T3 or T4 at 10(-7) M inhibited the basal- and ACTH-stimulated levels of intracellular cAMP. Physiological doses of T3 and T4 decreased the activities of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase. These results suggest that thyroid hormones counteract ACTH in adrenal steroidogenesis through their inhibition of cAMP production in ZFR cells.

Glucocorticoids and aging.

In this review we analyze the morphologic changes, hypothalamic-pituitary-adrenal (HPA) axis functions, glucocorticoid (GC) receptors, and steroidogenic enzyme activities in both animals and humans during aging. In rodent studies, older animals tend to show: 1) hypertrophy of adrenal zona fasciculata (ZF) cells; 2) neuronal loss in the hypothalamic area; 3) loss of GC receptors in the hippocampus; 4) raised circulating adrenocorticotropic hormone (ACTH) and GC levels, and increased release of corticotropin-releasing hormone from the hypothalamus; 5) reduced suppression of endogenous GC secretion after administration of dexamethasone; 6) decreased attenuation of response to chronic stress; and 7) increased activity of P450scc and 21-hydroxylase. According to the GC cascade hypothesis, stress and GCs facilitate the aging process in rats. Stress induces downregulation of GC receptors in the hippocampus, then impairs GC feedback on stress-induced HPA axis activation. Finally, an increase in the basal level of corticosterone and extended GC secretion following stress occurs. Because activation of the hippocampus decreases HPA axis function, the unrestrained elevation of GC concentration and the reduction in the level of GC receptors in the hippocampus may gradually weaken the feedback mechanisms and halt the response to stress. In humans, there are conflicting reports of HPA axis function during aging, so it is difficult to make a final conclusion regarding the relationship between aging and HPA axis function.

Inhibition of corticosterone secretion by thyroxine in male rats.

The effects of thyroxine (T4) on the secretion of corticosterone both in vivo and in vitro in male rats were studied. Rats were thyroidectomized (Tx) or sham Tx. The Tx rats were subcutaneously with T4 (20 micrograms/kg) or saline once daily for two weeks. In an in vitro experiment, adrenal glands were incubated with ACTH, T4, or ACTH plus T4 in the presence or absence of 0.5 mM 3-isobutyl-1-methylxanthine (IBMX) at 37 degrees C for 60 min. Medium and ether-extracted plasma samples were analyzed for corticosterone by radioimmunoassay (RIA). The accumulation of cyclic adenosine monophosphate (cAMP) in adrenal tissues after incubation with IBMX was measured by RIA. The levels of plasma corticosterone in Tx rats were significantly increased as compared with euthyroid rats. T4 replacement in Tx rats restored plasma corticosterone to euthyroid level. Administration of T4 in vitro resulted in an inhibition of both basal and ACTH-stimulated release of corticosterone. Both basal and ACTH-stimulated generations of cAMP in adrenal tissues were decreased by T4. These results suggest that T4 inhibits the spontaneous and ACTH-stimulated secretion of corticosterone by acting directly at adrenal glands via a decrease in cAMP production.

The role of cyclic AMP production, calcium channel activation and enzyme activities in the inhibition of testosterone secretion by amphetamine.

1. The aim of this study was to investigate the mechanism by which amphetamine exerts its inhibitory effect on testicular interstitial cells of male rats. 2. Administration of amphetamine (10(-12)-10(-6) M) in vitro resulted in a dose-dependent inhibition of both basal and human chorionic gonadotropin (hCG, 0.05 iu ml(-1))-stimulated release of testosterone. 3. Amphetamine (10(-9) M) enhanced the basal and hCG-increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in vitro (P<0.05) in rat testicular interstitial cells. 4. Administration of SQ22536, an adenylyl cyclase inhibitor, decreased the basal release (P<0.05) of testosterone in vitro and abolished the inhibitory effect of amphetamine. 5. Nifedipine (10(-6) M) alone decreased the secretion of testosterone (P<0.01) but it failed to modify the inhibitory action of amphetamine (10(-10)-10(-6) M). 6. Amphetamine (10(-10)-10(-6) M) significantly (P<0.05 or P<0.01) decreased the activities of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450c17, and 17-ketosteroid reductase (17-KSR) as indicated by thin-layer chromatography. (t.l.c.). 7. These results suggest that increased cyclic AMP production, decreased Ca2+ channel activity and decreased activities of 3beta-HSD, P450c17, and 17-KSR are involved in the inhibition of testosterone production induced by the administration of amphetamine.

The absence of influence of chronic hyperinsulinemia on the development of renovascular hypertension in rats.

Our previous studies have shown that sustained hyperinsulinemia increases blood pressure in rats. The precise mechanism is still unclear. The present study was conducted to assess if hyperinsulinemia could interact with angiotensin II and other pressor stimuli to increase blood pressure in renovascular hypertensive rats. Intact and uninephrectomized Sprague-Dawley rats with unilateral renal arterial constriction (2-kidney, 1 clip and 1-kidney, 1 clip Goldblatt rats) were administered insulin (3 mU/kg/min) for 6-12 weeks. The clipped rats without insulin infusion and normal rats served as controls. Changes in blood pressure were measured by tailcuff method without preheating. Results showed that either sustained infusion of insulin or renal arterial clipping alone in normal rats significantly increased the blood pressure. Superimposed infusion of insulin for 6-7 weeks into rats with unilateral renal artery constriction in either 2-kidney or 1-kidney model did not accelerate nor exacerbate the development of hypertension. There were no significant differences in body weight and plasma levels of glucose, triglycerides, sodium and potassium between 2-kidney, 1 clip Goldblatt hypertensive rats with and without insulin infusion. These data suggest that chronic hyperinsulinemia and angiotensin II do not act synergistically to increase the blood pressure in rats.

Renal dopamine not renal nerve mediates diuretic and natriuretic effect of ANF in rats.

Our previous study demonstrated that acutely or chronically unilateral renal denervation did not blunt intravenous ANF--induced hypotensive and ipsilateral renal effects. The present study was further to examine the permissive role of renal nerve and dopamine in the renal action of ANF. Experiments were conducted on anesthetized rats with either acute unilateral ureter ligation (n = 8), reserpine pretreatment (10 mg/kg, n = 7), mechanically controlled renal arterial pressure (n = 8) or blockade of dopamine D1 receptors by SCH23390 (n = 8, 0.8 micrograms/kg.min). The arterial blood pressure and renal clearance responses to intravenous (0.30-0.45 micrograms/kg.min) or intrarenal (0.10-0.15 micrograms/kg.min) infusion of ANF were measured. The results showed that unilateral ligation of the ureter to physiologically inhibit the contralateral renal efferent nerve activity did not alter the depressor, diuretic and natriuretic effects of ANF. Reserpine pretreatment blunted the diuretic and natriuretic response to intravenous administration of ANF. However, ANF-induced diuresis and natriuresis was persistently observed in both kidneys of rats with the left renal arterial pressure being controlled at a level comparable to that seen in the reserpine-pretreated group. Blockade of intrarenal dopamine D1 receptors by SCH23390 completely abolished the diuretic and natriuretic response to intrarenal infusion of ANF. These results support the notion that the diuretic and natriuretic effect of ANF is not resulted from a decrease in renal sympathetic efferent nerve activity, and further indicate that a mechanism associated with activation of the renal dopamine D1 receptors mediates the renal effect of ANF in rats.

Role of renal nerves in the hypotensive and the renal effects of atrial natriuretic factor in rats.

Our earlier studies have demonstrated that atrial natriuretic factor (ANF) can produce hypotensive, natriuretic and diuretic effects and that changes in the renal nerve activity can alter the renal excretory function. A few previous studies suggested that ANF could change the renal nerve activity. Thus, the present study was designed to assess the role of the renal nerve in the natriuretic and diuretic effect of ANF. Experiments were conducted on four groups of anesthetized Sprague-Dawley rats: normal control rats, unilateral acute renal denervated rats with and without ANF administration and chronic renal denervated rats. The arterial blood pressure and the renal function responses to intravenous infusion of graded doses of ANF (atriopeptin III. 0.15, 0.30 and 0.45 microgram/kg.min) were studied. In normal rats, infusion of ANF significantly decreased the mean arterial blood pressure in a dose-related pattern (from 109 +/- 2 to 107 +/- 3, 102 +/- 4 and 89 +/- 5 mmHg, respectively). The glomerular filtration rate (GFR) did not change significantly whereas the urine flow and the absolute and the fractional excretion rates of sodium and potassium were significantly increased. Renal denervation alone did not change the blood pressure and GFR, but produced ipsilateral diuresis and saluresis without changing the function of the contralateral kidney. Subsequent administration of ANF decreased the blood pressure but did not affect bilateral GFR. There were significant increments in the urine flow and the excretions of sodium and potassium in both the denervated and the contralateral kidneys. Infusion of ANF into chronic renal denervated rats also reduced the blood pressure and increased the renal excretion of water and sodium. These results indicate that the diuretic and the natriuretic effects of ANF is not resulted from a decreased activity of the renal efferent nerve and that the hypotensive and the renal effects of ANF are independent of renal innervation.