Atrial natriuretic peptide during water deprivation or hemorrhage in rats. Relationship with arginine vasopressin and osmolarity.

The concentrations of atrial natriuretic peptide (ANP) in atria, hypothalami and plasma were investigated in relation to the variations of the plasma endogenous immunoreactive arginine vasopressin (Ir-AVP) during water deprivation or hemorrhage in normal conscious Wistar rats. Furthermore, the in vitro and in vivo effect of extracellular hyperosmolarity on ANP release from right atrium and hypothalamus was examined. Water deprivation elevated circulating immunoreactive ANP (Ir-ANP: pg/ml) to 153 +/- 7 (24 h); 174 +/- 1 (48 h) from the control level (109.6 +/- 7.8). This increase in Ir-ANP concentration which correlated with atrial (r = -0.93) or hypothalamic (r = -0.87) Ir-ANP content decrease, was associated with significantly enhanced levels of plasma Ir-AVP, plasma sodium, osmolarity and hematocrit. An acute volume depletion by hemorrhage significantly reduced plasma Ir-ANP (67 +/- 8.4 pg/ml) from the sham operated level (140 +/- 18 pg/ml). Plasma Ir-AVP was elevated dramatically (207.4 +/- 53.4 pg/ml) compared with the sham operated level (8.8 +/- 2.6 pg/ml). These results, indicating the lack of correlation between plasma Ir-ANP and Ir-AVP in vivo, suggest that the ANP secretion, which is regulated mainly by plasma volume, may be modulated by a change in plasma osmolarity. Extracellular hyperosmolarity stimulated the ANP release from superfused sliced normal rat atria and hypothalami.     

Effects of noradrenaline administration on the interrenal gland of the newt, Triturus carnifex: evidence of intra-adrenal paracrine interactions

The existence of paracrine control of steroidogenic activity by adrenochromaffin cells in Triturus carnifex was investigated by in vivo noradrenaline (NA) administration. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the serum levels of aldosterone, NA, and adrenaline (A). In March and July, NA administration increased aldosterone release (from 187.23 +/- 2.93 pg/ml to 878.31 +/- 6.13 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 622.51 +/- 2.65 pg/ml in July) from steroidogenic cells. The cells showed clear signs of stimulation, as evidenced by a strong reduction of lipid content. Moreover, NA administration decreased the mean total number of secretory vesicles in the chromaffin cells in March (from 7.24 +/- 0.18 granules/micro2 to 5.57 +/- 1.88 granules/micro2) and July (from 7.74 +/- 0.74 granules/micro2 to 6.04 +/- 1.13 granules/micro2). In March, however, when T. carnifex chromaffin cells contain both catecholamines, NA (3.88 +/- 0.13 granules/micro2) and A (3.36 +/- 0.05 granules/micro2) in almost equal quantities, NA administration reduced A content (1.29 +/- 1.04 granules/micro2) in the chromaffin cells, enhancing adrenaline secretion (from 681.27 +/- 1.83 pg/ml to 1527.02 +/- 2.11 pg/ml). In July, when the chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/micro2; A: 0.32 +/- 0.13 granules/micro2), NA administration reduced the number of NA granules (5.45 +/- 1.10 granules/micro2), thereby increasing noradrenaline release from the chromaffin cells (from 640.19 +/- 1.65 pg/ml to 1217.0 +/- 1.14 pg/ml). The results of this study indicate that NA influences the steroidogenic cells, eliciting aldosterone release. Noradrenalin effects on the chromaffin cells, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the steroidogenic cells. The existence of intra-adrenal paracrine interactions in T. carnifex is discussed.     

Effects of adrenaline administration on the interrenal gland of the newt, Triturus carnifex: evidence of intraadrenal paracrine interactions

The existence of paracrine control of steroidogenic activity by adrenochromaffin cells in Triturus carnifex was investigated by in vivo adrenaline (A) administration. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the serum levels of aldosterone, noradrenaline (NA), and adrenaline. In March and July, adrenaline administration reduced aldosterone release (from 187.23 +/- 2.93 pg/ml to 32.28 +/- 1.85 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 87.51 +/- 2.57 pg/ml in July) from steroidogenic cells. The cells showed clear signs of lowered activity: they appeared full of lipid, forming large droplets. Moreover, adrenaline administration decreased the mean total number of secretory granules in the chromaffin cells in July (from 7.74 +/- 0.74 granules/microm(2) to 5.14 +/- 1.55 granules/microm(2)). In this period T. carnifex chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/microm(2); A: 0.32 +/- 0.13 granules/microm(2)). Adrenaline administration reduced noradrenaline content (4.36 +/- 1.40 granules/microm(2)) in the chromaffin cells, enhancing noradrenaline secretion (from 640.19 +/- 1.65 pg/ml to 1030.16 +/- 3.03 pg/ml). In March, adrenaline administration did not affect the mean total number of secretory vesicles (from 7.24 +/- 0.18 granules/microm(2) to 7.25 +/- 1.97 granules/microm(2)). In this period the chromaffin cells contain both catecholamines, noradrenaline (3.88 +/- 0.13 granules/microm(2)), and adrenaline (3.36 +/- 0.05 granules/microm(2)), in almost equal quantities; adrenaline administration reduced adrenaline content (1.74 +/- 0.84 granules/microm(2)), increasing adrenaline release (from 681.27 +/- 1.83 pg/ml to 951.77 +/- 4.11 pg/ml). The results of this study indicate that adrenaline influences the steroidogenic cells, inhibiting aldosterone release. Adrenaline effects on the chromaffin cells (increase of noradrenaline or adrenaline secretion) vary according to the period of chromaffin cell functional cycle. The existence of intraadrenal paracrine interactions in T. carnifex is discussed.     

Release of aldosterone and catecholamines from the interrenal gland of Triturus carnifex in response to adrenocorticotropic hormone (ACTH) administration

The influence of adrenocorticotropic hormone (ACTH) on the interrenal gland of Triturus carnifex was investigated by in vivo administration of synthetic ACTH. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the circulating serum levels of aldosterone, noradrenaline (NA), and adrenaline (A). In June and November, ACTH administration increased aldosterone release (from 281.50 +/- 1.60 pg/ml in carrier-injected newts to 597.02 +/- 3.35 pg/ml in June; from 187.45 +/- 1.34 pg/ml in carrier-injected animals to 651.00 +/- 3.61 pg/ml in November). The steroidogenic cells showed clear signs of stimulation, together with a reduction of lipid content in June and an increase of lipid content in November. Moreover, ACTH administration decreased the mean total number of secretory vesicles in the chromaffin cells in June (from 7.73 +/- 0.60 granules/microm2 in carrier-injected animals to 5.91 +/- 0.40 granules/microm2) and November (from 7.78 +/- 0.75 granules/microm2 in carrier-injected newts to 4.87 +/- 0.40 granules/microm2). In June, however, when T. carnifex chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/microm2; A: 0.32 +/- 0.13 granules/microm2), ACTH decreased NA content (5.52 +/- 0.32 granules/microm2) increasing NA release (from 639.82 +/- 3.30 pg/ml in carrier-injected to 880.55 +/- 4.52 pg/ml). In November, when both catecholamines, NA (3.92 +/- 0.34 granules/microm2) and A (3.84 +/- 0.33 granules/microm2), are present in the chromaffin cells, ACTH administration reduced A content (1.02 +/- 0.20 granules/microm2), enhancing adrenaline secretion (from 681.30 +/- 3.62 pg/ml in carrier-injected newts to 1,335.73 +/- 9.03 pg/ml). The results of this study indicate that ACTH influences the steroidogenic tissue, eliciting aldosterone release. The effects on the chromaffin tissue, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the increase of aldosterone release. Finally, the lack of an increase of A content in the chromaffin cells, or A serum level, following ACTH administration in June might suggest an independence of PNMT enzyme on corticosteroids.     

Effects of different angiotensins during acute,double blockade of the renin system in conscious dogs

Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol.kg-1.min-1) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol.kg-1.min-1). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 +/- 19 and 274 +/- 13 ml.kg-1.min-1, respectively) than for ANG II (107 +/- 13 ml.kg-1.min-1). ANG II increased ANG IR by 60 +/- 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 +/- 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 +/- 2 to 33 +/- 2 ml/min), sodium excretion (50 +/- 7 to 16 +/- 4 micromol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 +/- 8 to 19 +/- 3 micromol/min) and aldosterone secretion (to 268 +/- 71 pg/ml) at much lower ANG IR increments ( approximately 1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved.     

Vasopressin inhibits diuresis induced by water immersion in humans.

We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2-receptor agonist, could inhibit the diuresis induced by water immersion in humans. Water and electrolyte excretion, plasma atrial natriuretic factor concentration, and plasma aldosterone concentration were measured initially and after 3 h of water immersion in 13 healthy sodium-replete men given either placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic monophosphate and urea excretion and urine osmolality were also determined. DDAVP inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05). After 3 h of water immersion, plasma atrial natriuretic factor concentrations were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14 +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic factor concentrations, which should increase sodium excretion, DDAVP decreased the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05). DDAVP may be used to prevent the diuresis associated with central redistribution of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some Effects of a Low Sodium Diet High in Potassium on the Renin-Angiotensin System and Plasma Electrolyte Concentrations in Normal Dogs

Eight normal male Beagle dogs received 0.7 mmol Na+/kg/day for 5 weeks and 4.0 mmol Na+/kg/day in one 3 week control period preceding and another similar period following the low sodium period. The dogs received 6.8 mmol K+/kg/day throughout the study. The median plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were higher in the low sodium period than in the following control period (0.67 versus 0.28 ng/ml/h, p < 0.0001) and (204 versus 31 pg/ml, p < 0.0001). PRA and PAC quickly stabilized on a new steady level in response to altered intake of sodium chloride. The angiotensin-converting enzyme (ACE) activity was not changed by the altered intake of sodium chloride. The plasma concentrations of sodium and chloride were increased during the low sodium period. This could be due to an indirect effect of the high potassium intake of the dogs. Potassium leads to an increased secretion of aldosterone and thereby to an increased retention of sodium and chloride in the kidney. The possible implications of a high potassium content in a low sodium diet are discussed.     

Role of atrial natriuretic peptide in mineralocorticoid escape phenomenon in patients with primary aldosteronism

The withdrawal effect of spironolactone treatment on natriuresis was studied in relation to atrial natriuretic peptide (ANP) in five patients with primary aldosteronism due to adenoma. The patients had been treated with spironolactone for 2-3 months before they were admitted. After admission, blood pressure, body weight, and urinary excretion of sodium were measured daily. Venous samples were obtained twice a week for measurements of plasma levels of ANP, plasma renin activity (PRA), and plasma concentrations of aldosterone (PAC), cortisol, and deoxycorticosterone. The study was performed for 7 days during the treatment with spironolactone and for 18 days after stopping the administration. Plasma volume was determined two times, during the control period and on the 13th day after stopping spironolactone. Urinary sodium excretion decreased initially and returned to the control levels successively. Body weight and plasma volume increased, and blood pressure rose steadily. PRA and the plasma concentrations of cortisol and deoxycorticosterone decreased significantly (P less than 0.05); however, high levels of PAC did not alter significantly. Plasma ANP levels increased significantly (P less than 0.05) from 26 +/- 4 pg/ml during the control period to 195 +/- 47 pg/ml on the 13th day after stopping spironolactone. The data of the urinary sodium excretion showed the escape from sodium-retaining effect of aldosterone, and this escape could be explained by the increase in plasma ANP. Furthermore, ANP might contribute to the decrease in cortisol and deoxycorticosterone in plasma because of the direct inhibitory action of ANP on steroidogenesis.     

Cellular localization, half-life, and secretion of peptide YY

Tissue and plasma concentration of peptide YY (PYY) were measured by means of a radioimmunoassay (RIA) developed in our laboratory, using a specific PYY antiserum generated in New Zealand white rabbits against synthetic PYY, and dextran-coated charcoal to terminate the assay. Cellular localization of PYY was studied immunohistochemically using the peroxidase-antiperoxidase (PAP) technique. The highest tissue concentration of PYY was found in the mucosa of the terminal ileum and colon. PYY-containing secretory granules were primarily found in the basal pole of open-type endocrine cells. Basal plasma concentration of PYY was 70 +/- 9 pg/ml and rose to 357 +/- 30 pg/ml during the IV administration of PYY at 400 pmol/kg-h. A significant correlation was found (r = 0.94, p less than 0.05) between dose of PYY (12.5, 25, 50, 100, 200, 400 pmol/kg-h, IV) and plasma concentration of PYY. The calculated half-life of PYY in plasma was 8.3 +/- 1.9 minutes. Plasma concentration of PYY during the intraduodenal administration of sodium oleate (150 +/- 20 pg/ml) or long-chain triglyceride (187 +/- 37 pg/ml) was similar to plasma concentration of PYY obtained during the IV administration of PYY at 100 pmol/kg-h. Plasma concentration of PYY raised (126 +/- 10 pg/ml) after the administration of bombesin (400 pmol/kg-h, IV). Bile enhanced release of PYY. The present study suggests a hormonal role for PYY.     

Haemodynamic effects of angiotensin II in conscious, non-ascitic cirrhotic rats

The effect of angiotensin II (AII) on systemic and regional haemodynamics was studied in 18 control and 18 cirrhotic, non-ascitic conscious rats (CCl4/phenobarbital model). Cirrhotic rats were found to retain sodium and to have normal plasma renin and plasma aldosterone concentrations when compared with control animals. Cirrhotic rats showed an enhanced cardiac output (34.4 +/- 0.5 vs. 27.5 +/- 2.0 ml/min in controls) and decreased peripheral resistances (2.96 +/- 0.25 vs. 3.95 +/- 0.31 mm Hg/min/100 g/ml in controls) under basal conditions. When AII was administered cardiac output decreased by 10.7 +/- 1.2% in cirrhotic rats, whereas it increased in control animals (11.2 +/- 2%, p less than 0.005). The AII-induced increase in arterial pressure was lower in cirrhotic than in control rats. The renal blood supply was particularly impaired by AII in cirrhotics, with a maintained flow to other organs (muscle, testes). It is concluded that the response to AII is disturbed in rats with hepatic cirrhosis even in a stage without ascites and with plasma renin and aldosterone concentrations similar to those of control animals.     

Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives

Angiotensin (Ang) II induces oxidative stress in vitro and in animal models of hypertension. We tested the hypothesis that Ang II increases oxidative stress in human hypertension, as assessed by plasma F2-isoprostane concentrations. Plasma F2-isoprostanes, hemodynamic and endocrine parameters were measured at baseline and following a 55 min infusion of 3 ng/kg/min Ang II in 13 normotensive and 13 hypertensive volunteers ingesting a high- (200 mmol/d) or low- (10 mmol/d) sodium diet. Mean arterial pressure (MAP) and body mass index were higher in hypertensive subjects. Ang II infusion increased MAP (p<.001) and plasma aldosterone concentrations (p<.001) and decreased plasma renin activity (p<.001) and renal plasma flow (p<.001) to a similar extent in both groups. Plasma F2-isoprostane concentrations were similar at baseline. There was no effect of Ang II on F2-isoprostane concentrations during low-salt intake in either group (normotensive 51.7 +/- 7.1 to 53.7 +/- 6.5 pg/ml and hypertensive 52.2 +/- 8.2 to 56.2 +/- 10.0 pg/ml; mean +/- SE). During high-salt intake, Ang II increased F2-isoprostane concentrations in the hypertensive group (52.3 +/- 7.2 to 63.2 +/- 10.4 pg/ml, p=0.010) but not in the normotensive group (54.2 +/- 4.4 to 58.9 +/- 6.6 pg/ml, p=0.83). Acute Ang II infusion increases oxidative stress in vivo in hypertensive humans. The renin-angiotensin system may contribute to oxidative stress in human cardiovascular disease.     

Role of the renin-angiotensin system during alterations of sodium intake in conscious mice

The present studies were performed to quantify circulating components of the renin-angiotensin-aldosterone axis and to determine the functional importance of this system during alterations in sodium intake in conscious mice. Increasing sodium intake from approximately 200 to 1,000 microeq/day significantly decreased plasma renin concentration from 472 +/- 96 to 304 +/- 83 ng ANG I. ml(-1). h(-1) (n = 5) but did not alter plasma renin activity from the low-sodium level of 7.7 +/- 1.1 ng ANG I. ml(-1). h(-1). Despite the elevated plasma renin concentration, plasma ANG II in mice on low-sodium level averaged 14 +/- 3 pg/ml and was significantly suppressed to 6 +/- 1 pg/ml by high-sodium intake (n = 7). Consistent with the modulation of ANG II, plasma aldosterone significantly decreased from 41 +/- 8 to 8 +/- 3 ng/dl when sodium intake was elevated (n = 6). In a final set of experiments, the continuous infusion of ANG II (20 ng. kg(-1). min(-1)) led to a mild salt-sensitive increase in mean arterial pressure from 108 +/- 2 to 131 +/- 2 mmHg as sodium intake was varied from low to high (n = 7). In vehicle-infused mice, mean arterial pressure was unaltered from 109 +/- 2 mmHg when sodium intake was increased (n = 6). These studies indicate that the physiological suppression of circulating ANG II may be required to maintain a constancy of arterial pressure during alterations in sodium intake in normal mice.     

Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.     

Natriuresis induced by mild hypernatremia in humans

The hypothesis that increases in plasma sodium induce natriuresis independently of changes in body fluid volume was tested in six slightly dehydrated seated subjects on controlled sodium intake (150 mmol/day). NaCl (3.85 mmol/kg) was infused intravenously over 90 min as isotonic (Iso) or as hypertonic saline (Hyper, 855 mmol/l). After Hyper, plasma sodium increased by 3% (142.0 +/- 0.6 to 146.2 +/- 0.5 mmol/l). During Iso a small decrease occurred (142.3 +/- 0.6 to 140.3 +/- 0.7 mmol/l). Iso increased estimates of plasma volume significantly more than Hyper. However, renal sodium excretion increased significantly more with Hyper (291 +/- 25 vs. 199 +/- 24 micromol/min). This excess was not mediated by arterial pressure, which actually decreased slightly. Creatinine clearance did not change measurably. Plasma renin activity, ANG II, and aldosterone decreased very similarly in Iso and Hyper. Plasma atrial natriuretic peptide remained unchanged, whereas plasma vasopressin increased with Hyper (1.4 +/- 0.4 to 3.1 +/- 0.5 pg/ml) and decreased (1.3 +/- 0.4 to 0.6 +/- 0.1 pg/ml) after Iso. In conclusion, the natriuretic response to Hyper was 50% larger than to Iso, indicating that renal sodium excretion may be determined partly by plasma sodium concentration. The mechanism is uncertain but appears independent of changes in blood pressure, glomerular filtration rate, the renin system, and atrial natriuretic peptide.     

Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone,StAR, and PBR

The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 +/- 1.4 ng/ml; n = 12) and ACTH-stimulated (94.0 +/- 9.4 ng/ml; n = 14) corticosterone levels compared with normoxic controls (basal = 8.3 +/- 0.5 ng/ml; n = 11; stimulated = 51.3 +/- 3.8 ng/ml; n = 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 +/- 4 vs. 78 +/- 8 pg/ml) or after (481 +/- 73 vs. 498 +/- 52 pg/ml) porcine ACTH injection (20 microg/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1alpha mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate.     

Obesity-induced hypertension develops in young rats independently of the renin-angiotensin-aldosterone system

A correlation exists between obesity and hypertension. In the currently available models of diet-induced obesity, the treatment of rats with a high fat (HF) diet does not begin until adulthood. Our aim was to develop and characterize a model of pre-pubescent obesity-induced hypertension. Male Sprague-Dawley rats were fed a HF diet (35% fat) for 10 weeks, beginning at age 3 weeks. Blood pressure was measured by tail-cuff, and a terminal blood sample was obtained to measure fasting blood glucose, insulin, plasma renin, aldosterone, thiobarbitutic acid reactive substances (TBARS), and free 8-isoprostanes levels. The vascular reactivity in the aorta was assessed using a myograph. Blood pressure was increased in rats fed the HF diet (HF, 161 +/- 2 mm Hg vs. control, 137 +/- 2 mm Hg, P < 0.05). Blood glucose (HF, 155 +/- 4 mg/dL vs. control, 123 +/- 5 mg/dL, P < 0.05), insulin (HF, 232 +/- 63 pM vs. control, 60 +/- 11 pM, P < 0.05), TBARS (expressed as nM of malondialdehyde [MDA]/ml [HF, 1.8 +/- 0.37 nM MDA/ml vs. control 1.05 +/- 0.09 nM MDA/ml, P < 0.05]), and free 8-isoprostanes (HF, 229 +/- 68 pg/ml vs. control, 112 +/- 9 pg/ml, P < 0.05) levels were elevated in the HF diet group. Interestingly, plasma renin and aldosterone levels were not different between the groups. The maximum vasoconstriction to phenylephrine (10(-4) M) was increased in the HF diet group (HF, 26.1 +/- 1.5 mN vs. control 22.3 +/- 1.2 mN, P < 0.05). In conclusion, pre-pubescent rats become hypertensive and have increased oxidative stress and enhanced vasoconstriction when fed a HF diet. Surprisingly, this occurs without the increase in renin or aldosterone levels seen in the adult models of diet-induced obesity.     

Effects of synthetic atrial natriuretic factor (ANF) on renin-aldosterone axis in the conscious newborn calf

The effects of synthetic atrial natriuretic factor (ANF) on the renin-aldosterone axis were studied in fifteen 4-7 day-old male milk-fed calves divided into 3 groups of 5 animals each. Synthetic ANF intravenous (i.v.) administration (1.6 micrograms/kg body wt over 30 min) induced a transient significant fall in plasma renin activity (from 2.5 +/- 0.3 to 1.7 +/- 0.3 ng angiotensin l/ml/h; P less than 0.05) but failed to reduce basal plasma aldosterone levels in the first group of animals. Administration (i.v.) of angiotensin II (AII) (0.8 micrograms/kg body wt for 75 min) was accompanied by a progressive fall in plasma renin activity (from 2.2 +/- 0.3 to 0.8 +/- 0.1 ng angiotensin l/ml/h; P less than 0.01) and by an increase in plasma aldosterone levels (from 55 +/- 3 to 86 +/- 5 pg/ml; P less than 0.01) both in the second and the third groups; addition of ANF to AII infusion (AII: 0.5 mu/kg body wt for 45 min; AII: 0.3 micrograms/kg body wt and ANF 1.6 micrograms/kg body wt during 30 min) in the third group did not modify plasma renin activity or AII-stimulated plasma aldosterone levels when compared to the AII-treated group. These findings show that in the newborn calf ANF is able to reduce plasma renin activity but fails to affect basal and AII-stimulated plasma aldosterone levels, suggesting that the zona glomerulosa of the newborn adrenal cortex is insensitive to a diuretic, natriuretic and hypotensive dose of the atrial peptide.     

Nifedipine inhibits the hypoxia-induced decrease in plasma renin activity in conscious dogs.

Acute hypoxia induces a decrease in plasma renin activity (PRA), mediated, e.g., by an increase in adenosine concentration, calcium channel activity, or inhibition of ATP-sensitive potassium channels. The decrease in PRA results in a decrease in angiotensin II (AngII) and plasma aldosterone concentration (PAC). This study investigates whether these hypoxia-induced mechanisms can be inhibited by the L-type voltage-dependent calcium channel antagonist nifedipine. Eight conscious, chronically tracheotomized dogs received a low sodium diet (0.5 mmol Na x kg body wt(-1) x day(-1)). The dogs were studied twice in randomized order, either with nifedipine infusion (1.5 microg x kg body wt(-1) x min(-1), Nifedipine) or without (Control). The dogs were breathing spontaneously: first hour, normoxia [inspiratory oxygen fraction (FiO2)=0.21]; second and third hour hypoxia (FiO2=0.1). In Controls, PRA (6.8+/-0.8 vs. 3.0+/-0.5 ngAngI x ml(-1) x min(-1)), AngII (13.3+/-1.9 vs. 7.3+/-1.9 pg/ml), and PAC (316+/-50 vs. 69+/-12 pg/ml) decreased during hypoxia (P<0.05). In Nifedipine experiments, PRA (6.5+/-0.9 vs. 10.5+/-2.4 ngAngI x ml(-1) x min(-1)) and AngII (14+/-1.1 vs. 18+/-3.9 pg/ml) increased during hypoxia, whereas the decrease in PAC (292+/-81 vs. 153+/-41 pg/ml) was blunted (P<0.05). These results foster the idea that the hypoxia-induced decrease in PRA involves L-type calcium channel activity.