Atrial natriuretic peptide relation to plasma and heart zinc concentrations of wistar rats exposed to cold and hot ambients

Plasma atrial natriuretic peptide (ANP) and zinc levels, as well as heart tissue zinc concentrations were determined, in male Wistar rats after the exposure of 114 rats at low temperature (4°C) and 95 rats at high temperature (35–36°C) for 28 d. Plasma ANP was estimated by radioimmunoassay and Zn²⁺ concentrations by atomic absorption spectrometry. Values were compared to a control group exposed at 20–22°C (76 rats). Plasma ANP and Zn²⁺ levels, as well as heart tissue Zn²⁺ concentrations of control rats did not show statistically significant variations during the study, whereas rats exposed to cold and hot ambients showed significant variations of the parameters. A significant increase of plasma ANP and plasma zinc and heart tissue Zn²⁺ concentrations developed during cold exposure, whereas a gradual decrease of plasma ANP and Zn²⁺ levels was revealed during hot adaptation. Results also indicate that plasma ANP and zinc levels are proportionally related, whereas there is an inverse relationship between plasma ANP levels and heart Zn²⁺ concentrations, in both cold and hot exposed rats. In conclusion, our results show that ANP in relation to zinc probably play an important role in cold and hot acclimatization of rats.     

Plasma atriopeptin response to prolonged cycling in humans.

The exercise-induced increase in plasma atriopeptin (ANP) has been related to exercise intensity. The independent effect of duration on the ANP response to dynamic exercise remains incompletely documented. The purpose of this study was to describe the time course of plasma ANP concentration during a 90-min cycling exercise protocol and to examine this in light of concurrent variations in plasma arginine vasopressin (AVP), aldosterone (ALD), and catecholamine (norepinephrine and epinephrine) concentrations as well as plasma renin activity (PRA). Seven male and four female healthy college students (23 +/- 2 yr) completed a prolonged exercise protocol on a cycle ergometer at an intensity of 67% of maximal O2 uptake. Venous blood was sampled through an indwelling catheter at rest, after 15, 30, 45, 60, and 90 min of exercise, and after 30 min of passive upright recovery. Results (means +/- SE) indicate an increase in ANP from rest (22 +/- 2.6 pg/ml) at 15 min of exercise (45.3 +/- 7.4 pg/ml) with a further increase at 30 min (59.4 +/- 9.8 pg/ml) and a leveling-off thereafter until completion of the exercise protocol (51.7 +/- 10.7 pg/ml). In plasma ALD and PRA, a significant increase was found from rest (ALD, 21.4 +/- 6.4 ng/dl), PRA, 2.5 +/- 0.5 ng.ml-1.h-1 after 30 min of cycling, which continued to increase until completion of the exercise (ALD 46.6 +/- 8.7 ng/dl, PRA 9.5 +/- 0.9 ng.ml-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulation of brain mast cells by compound 48/80, a histamine liberator, evokes renin and vasopressin release in dogs

Because degranulation of brain mast cells activates adrenocortical secretion (41, 42), we examined whether activation of such cells increases renin and vasopressin (antidiuretic hormone: ADH) secretion. For this, we administered compound 48/80 (C48/80), which liberates histamine from mast cells, to pentobarbital-anesthetized dogs. An infusion of 37.5 microg/kg C48/80 into the cerebral third ventricle evoked increases in plasma renin activity (PRA), and in plasma epinephrine (Epi) and ADH concentrations. Ketotifen (mast cell-stabilizing drug; given orally for 1 wk before the experiment) significantly reduced the C48/80-induced increases in PRA, Epi, and ADH. Resection of the bilateral splanchnic nerves (SPX) below the diaphragm completely prevented the C48/80-induced increases in PRA and Epi, but potentiated the C48/80-induced increase in ADH and elevated the plasma Epi level before and after C48/80 challenge. No significant changes in mean arterial blood pressure, heart rate, concentrations of plasma electrolytes (Na+, K+, and Cl-), or plasma osmolality were observed after C48/80 challenge in dogs with or without SPX. Pyrilamine maleate (H1 histaminergic-receptor antagonist) significantly reduced the C48/80-induced increase in PRA when given intracerebroventricularly, but not when given intravenously. In contrast, metiamide (H2 histaminergic-receptor antagonist) given intracerebroventricularly significantly potentiated the C48/80-induced PRA increase. A small dose of histamine (5 microg/kg) administered intracerebroventricularly increased PRA twofold and ADH fourfold (vs. their basal level). These results suggest that in dogs, endogenous histamine liberated from brain mast cells may increase renin and Epi secretion (via the sympathetic outflow) and ADH secretion (via the central nervous system).     

Volume Regulation and Renal Function at High Altitude across Gender

Aims

We investigated changes in volume regulating hormones and renal function at high altitudes and across gender.

Methodology

Included in this study were 28 subjects (n = 20 males; n = 8 females. ages: 19 – 65 yrs), who ascended to a height of 3440m (HA1), on the 3^rd day and to 5050m (HA2), on the 14^th day. Plasma and urinary creatinine and urinary osmolality as well as plasma levels of plasma renin activity (PRA), Aldosterone, antidiuretic hormone (ADH), and atrial natriuretic peptide (ANP) were measured. The plasma volume loss (PVL) was estimated from plasma density and hematocrit. Glomerular filtration rate (GFR) was measured based on nocturnal (9 hour) creatinine clearance; this was compared with various methods for estimation of GFR.

Results

The mean 24-hour urine production increased significantly in both sexes across the expedition. But PVL reached significance only in males. No changes in Na⁺ in plasma, urine or its fractional excretion were seen at both altitudes. Urinary osmolality decreased upon ascent to the higher altitudes. ADH and PRA decreased significantly at both altitudes in males but only at HA2 in females. However, no changes in aldosterone were seen across the sexes and at different altitudes. ANP increased significantly only in males during the expedition. GFR, derived from 9-h creatinine clearance (CreaCl), decreased in both sexes at HA1 but remained stable at HA2. Conventional Crea[p]-based GFR estimates (eGFR) showed only poor correlation to CreaCl.

Conclusions

We report details of changes in hormonal patterns across high altitude sojourn. To our knowledge we are not aware of any study that has examined these hormones in same subjects and across gender during high altitude sojourn. Our results also suggest that depending on the estimation formula used, eGFR underestimated the observed decrease in renal function measured by CreaCl, thus opening the debate regarding the use of estimated glomerular filtration rates at high altitudes.     

Involvement of the atrial natriuretic peptide in the reduction of arterial pressure induced by swimming but not by running training in hypertensive rats

The aim of this study was to compare, under resting conditions, the influence of chronic training in swimming or running on mean arterial pressure (MAP) and the involvement of the natriuretic peptide system in this response. Two-month-old male spontaneously hypertensive rats (SHR) were divided into three groups—sedentary (SD), swimming (SW) and running (RN)—and were trained for eight weeks under regimens of similar intensities. Atria tissue and plasma atrial natriuretic peptide (ANP) concentrations were measured by radioimmunoassay. ANP mRNA levels in the right and left atria as well as the natriuretic peptide receptors (NPR), NPR-A and NPR-C, mRNA levels in the kidney were determined by real-time PCR. Autoradiography was used to quantify NPR-A and NPR-C in mesenteric adipose tissue. Both training modalities, swimming and running, reduced the mean arterial pressure (MAP) of SHR. Swimming, but not running, training increased plasma levels of ANP compared to the sedentary group (P < 0.05). Expression of ANP mRNA in the left atrium was reduced in the RN compared to the SD group (P < 0.05). Expression of NPR-A and NPR-C in the kidneys of the SW group decreased significantly (P < 0.05) compared to the SD group. Although swimming increased ¹²⁵I-ANP binding to mesenteric adipose tissue, displacement by c-ANF was reduced, indicating a reduction of NPR-C. These results suggest that the MAP reduction induced by exercise in SHR differs in its mechanisms between the training modalities, as evidenced by the finding that increased levels of ANP were only observed after the swimming regimen.     

Atrial natriuretic peptide and thyroid hormones’ relation to plasma and heart calcium and magnesium concentrations of wistar rats exposed to cold and hot ambients

Plasma ANP (atrial natriuretic peptide), thyroid hormones, and calcium and magnesium levels as well as heart tissue calcium and magnesium concentrations were determined in male Wistar rats after exposure of 114 rats at low temperature (4°C) and 95 rats at high temperature (35–36°C) for 28 d. Plasma ANP, triiodothyronine (T₃), thyroxine (T₄), thyroid-stimulating hormone (TSH), free T₃, and free T₄ were estimated by radioimmunoassay, and plasma and heart tissue levels of Ca and Mg by flame atomic absorption spectrophotometry. Results were compared to a control group exposed at 20–22°C (76 rats). All the above parameters in control rats did not show statistically significant variations during the study. A significant increase of plasma ANP, T₃, T₄, Ca, and Mg concentrations developed during cold exposure, whereas a gradual decrease of plasma ANP, T₃, T₄, and Mg concentrations was revealed during hot exposure. A significant increase of heart tissue Mg concentrations developed during hot exposure. Results also indicate that plasma ANP and T₃ levels are proportionally related, whereas an inverse relationship exists between plasma ANP and T₃ levels and heart Mg concentrations, in both cold and hot exposed rats. In conclusion, ANP and thyroid hormones in relation to Ca and Mg play an important role in temperature adaptation.     

Exaggerated ANF response to exercise in middle-aged vs. young runners

Hormonal, electrolyte, and renal responses were measured before, during, and after a marathon (42.2 km) in 14 runners: 8 young (Y) (mean age 27.8 yr) and 6 middle aged (MA) (mean aged 46.7 yr). No differences between groups in prerun values for heart rate (HR), plasma osmolality (OSM), antidiuretic hormone (ADH), aldosterone (ALDO), atrial natriuretic factor (ANF), or plasma renin activity (PRA) were found. Renal and urinary measurements were also similar between groups before the marathon. After 10 km of running, both groups had significant increases in HR, ALDO, ANF, and PRA, while OSM, Na+, and ADH remained unchanged from prerun values. The increase in plasma ANF concentrations at this point was significantly greater in the MA subjects compared with the Y (mean increase 104.1 vs. 42.8 pg/ml, respectively; P less than 0.01). Immediate postmarathon values for OSM, ADH, and Na+ were significantly higher than initial values in both groups, while HR, PRA, and ALDO continued to increase above the elevated levels found at 10 km. ANF values immediately postmarathon remained higher than prerun concentrations but were significantly reduced from those obtained at 10 km. In contrast, HR continued to rise until the completion of the run. These data are consistent with recent reports of an exaggerated ANF response in older subjects in response to central blood volume expansion.     

Influence of season on plasma antidiuretic hormone, angiotensin II, aldosterone and plasma renin activity in young volunteers

We investigated seasonal changes in hormonal and thermoregulatory responses. Eight volunteers were subjected to the experiment at four times of the year: around the vernal and autumnal equinoxes, and at the summer and winter solstices at latitude 35° N. Plasma antidiuretic hormone (ADH), angiotensin II (ANG II), aldosterone (ALD) and plasma renin activity (PRA) were analyzed before and after water immersion. Seasonal changes in thermoregulatory responses were assessed by measuring core temperature and sweat rate during immersion of the leg in hot water (at 42°C) for 30 min in a room maintained at 26°C. The concentration of plasma ADH and ALD before water immersion was significantly higher in summer than in other seasons. The concentrations of ANG II and PRA did not show seasonal variations. Changes in tympanic temperature during water immersion showed significant differences between seasons, and were higher in winter than in other seasons. The sweat rate was significantly higher in summer than in other seasons. In summary, ADH and ALD concentrations displayed a seasonal rhythm with marked elevation in summer; this may be a compensative mechanism to prevent dehydration from increased sweat loss during summer due to heat acclimatization.     

Modification of water and electrolyte metabolism during head-down tilting by hypoglycemia in men.

The effect of hypoglycemic stress on the changes in water and electrolyte metabolism induced by head-down tilting (HDT) was studied. Six healthy men were subjected to postural changes (30 min standing, 2 h HDT, 1 h standing), with or without the intravenous administration of insulin at the beginning of HDT. When insulin was not given, antidiuretic hormone (ADH), cortisol, plasma renin activity (PRA), aldosterone, and catecholamine levels were decreased and atrial natriuretic polypeptide (ANP) levels increased during HDT. These changes were associated with 2.5- and 1.5-fold increases in urine flow and sodium excretion, respectively, when compared with the amounts before HDT. On the other hand, insulin-induced hypoglycemia during HDT produced increases in ADH, cortisol, PRA, aldosterone, and catecholamine levels. At the same time, an exaggerated ANP response by HDT was observed. These hormonal changes were associated with an abolishment of the increases in urine flow and sodium excretion. It is suggested that acute stress modifies the changes in fluid and electrolyte metabolism induced by HDT.     

Circulating endothelin parallels arterial blood pressure during sleep in healthy subjects

OBJECTIVE: To characterize plasma endothelin 1 (ET-1) and arterial blood pressure (ABP) time courses during the first complete non-rapid eye movement (NREM)-REM sleep cycle in healthy subjects, together with plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP). METHODS: Heart rate (HR), intra-arterial blood pressure and sleep electroencephalographic activity were recorded continuously during the night in eight healthy 20-28-year-old males. Blood was sampled every 10 min during their first complete sleep cycle for simultaneous measurements of plasma ET-1, PRA and ANP. RESULTS: Circulating ET-1 demonstrated significant variations during the sleep cycle (p<0.0001) that paralleled those of ABP (p<0.05) and HR (p<0.005), with a minimum during NREM sleep and a maximum during REM sleep. ET-1 time course opposed that of PRA which increases during NREM sleep and decreases during REM sleep (p<0.0005). Plasma ANP did not demonstrate systematic variation in relation with the sleep cycle. CONCLUSION: Circulating ET-1, which parallels variations of ABP, may participate in ABP regulation during sleep in healthy subjects, in association with the renin-angiotensin system.     

Infusion of iso-rANP(1-45) or (17-45) increases plasma immunoreactive ANP and lowers plasma renin activity and aldosterone

We have reported that a second rat atrial natriuretic peptide, iso-rANP (1-45), as well as the putative ANP homologue, iso-rANP (17-45), elicited circulatory and renal responses in the rat similar to those found after administration of ANP. Iso-rANP also interacted with ANP to potentiate the observed biological activity in the rat. In the present studies in awake dogs, intravenous infusion of low doses (6.3-50 pmol.kg-1.min-1) of iso-rANP(1-45) and iso-rANP(17-45) increased plasma immunoreactive ANP and suppressed plasma renin activity (PRA) and aldosterone. Iso-rANP, like ring-deleted analogues of ANP, may have displaced ANP from ANP clearance receptors to increase plasma ANP concentration, since factors influencing myocardial ANP release were not changed. The effect of iso-rANP (1-45) and (17-45) in lowering PRA and plasma aldosterone may therefore have been indirect, via ANP stimulation of active guanylate cyclase-linked ANP receptors. However, an additional direct effect of iso-rANP on an active receptor cannot be excluded.     

Plasma renin activity, aldosterone and catecholamine levels when swimming and running

The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.     

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.     

Physiological variability of fluid-regulation hormones in young women.

We tested the physiological reliability of plasma renin activity (PRA) and plasma concentrations of arginine vasopressin (P[AVP]), aldosterone (P[ALD]), and atrial natriuretic peptide (P[ANP]) in the early follicular phase and midluteal phases over the course of two menstrual cycles (n = 9 women, ages 25 +/- 1 yr). The reliability (Cronbach's alpha >/=0.80) of these hormones within a given phase of the cycle was tested 1) at rest, 2) after 2.5 h of dehydrating exercise, and 3) during a rehydration period. The mean hormone concentrations were similar within both the early follicular and midluteal phase tests; and the mean concentrations of P[ALD] and PRA for the three test conditions were significantly greater during the midluteal compared with the early follicular phase. Although Cronbach's alpha for resting and recovery P[ANP] were high (0.80 and 0.87, respectively), the resting and rehydration values for P[AVP], P[ALD], and PRA were variable between trials for the follicular (alpha from 0.49 to 0.55) and the luteal phase (alpha from 0.25 to 0. 66). Physiological reliability was better after dehydration for P[AVP] and PRA but remained low for P[ALD]. Although resting and recovery P[AVP], P[ALD], and PRA were not consistent within a given menstrual phase, the differences in the concentrations of these hormones between the different menstrual phases far exceeded the variability within the phases, indicating that the low within-phase reliability does not prevent the detection of menstrual phase-related differences in these hormonal variables.     

Altered burst swimming in rainbow trout Oncorhynchus mykiss exposed to natural and synthetic oestrogens

Juvenile rainbow trout Oncorhynchus mykiss were exposed to two concentrations each of 17β‐oestradiol (E2; natural oestrogen hormone) or 17α‐ethinyl oestradiol (EE2; a potent synthetic oestrogen hormone) to evaluate their potential effects on burst‐swimming performance. In each of six successive burst‐swimming assays, burst‐swimming speed (U_burst) was lower in fish exposed to 0·5 and 1 µg l^?1 E2 and EE2 for four days compared with control fish. A practice swim (2 days prior to exposure initiation) in control fish elevated initial U_burst values, but this training effect was not evident in the 1 µg l^?1 EE2‐exposed fish. Several potential oestrogen‐mediated mechanisms for U_burst reductions were investigated, including effects on metabolic products, osmoregulation and blood oxygen‐carrying capacity. Prior to burst‐swimming trials, fish exposed to E2 and EE2 for 4 days had significantly reduced erythrocyte numbers and lower plasma glucose concentrations. After six repeated burst‐swimming trials, plasma glucose, lactate and creatinine concentrations were not significantly different among treatment groups; however, plasma Cl^? concentrations were significantly reduced in E2‐ and EE2‐treated fish. In summary, E2 and EE2 exposure altered oxygen‐carrying capacity ([erythrocytes]) and an osmoregulatory‐related variable ([Cl^?]), effects that may underlie reductions in burst‐swimming speed, which will have implications for fish performance in the wild.     

Comparison of the biological effects of two angiotensin II analogues in hypertensive patients with sodium depletion

The effects on blood pressure (BP), plasma aldosterone concentration (PAC) and plasma renin activity (PRA) of two angiotensin II analogues (AII A), i.e., 1-sarcosine, 8-isoleucine angiotensin II (Sar¹, I1e⁸-AII) and 1-sarcosine, 8-alanine angiotensin II (Sar¹, Ala⁸-AII), were investigated in patients with hypertension with various etiologies on sodium depletion. The changes of BP, PAC and PRA on infusion of Sar¹, Ile⁸-AII and Sar¹, Ala⁸-AII were very similar. With both compounds, there were significant inverse correlations between the pre-infusion PRA and the changes in BP and PAC, and a significant positive correlation between the pre-infusion PRA and change in PRA. The slopes of the regression lines for the correlations of changes in BP, PAC and PRA, plotted as functions of the pre-infusion PRA for Sar¹, Ile⁸-AII and Sar¹, Ala⁸-AII were not statistically different. In clinical investigations, the two compounds seemed equally useful for detecting renin-dependency in hypertension.     

Effects on ADH activity and distribution,following selection for tolerance to ethanol in Drosophila melanogaster

Strains of Drosophila melanogaster homozygous for either the Adh ^F or the Adh ^S allele were kept on food supplemented with ethanol for 20 generations. These strains (FE and SE) were tested for tolerance to ethanol and compared with control strains (FN and SN). The E strains showed increased tolerance to ethanol both in the adult and in the juvenile life stages. In adults the increase in tolerance was not accompanied by an increase in overall ADH activity. However, there were changes in the distribution of ADH over the body parts. Flies of the FE strain possessed significantly more ADH in the abdomen, compared with FN. Another set of FN and SN populations were started both on standard food and on ethanol food with reduced yeast concentrations. After 9 months ADH activities were determined in flies from these populations which had been placed on three different media: the food the populations had been kept on, regular food and regular food supplemented with ethanol. The phenotypic effects of yeast reduction on ADH activity were considerably, but longterm genetic effects were limited.     

Naloxone effect on ANP in trained and untrained rats

1. The effect of a dose of naloxone (1 mg·kg⁻¹ b.w.) on peripheral (plasma, atria) and central (hypothalamus, hypophysis) levels of atrial natriuretic peptide (ANP) was investigated in the rat.2. In control rats, an acute subcutaneous dose of naloxone produced no significant change in plasma ANP, but a decrease (NS) in atrial ANP concentration.3. In physically conditioned animals, naloxone produced a significant decrease in atrial ANP levels. Receptor sensitivity may thus be involved in this differential response.4. In hypothalamus and hypophysis, no effect on ANP concentrations was seen after a high dose of naloxone whether in control or in physically conditioned animals, suggesting peripheral and central ANP might be differently regulated, at least after chronic endurance physical training.     

Biological activity of des-(Asp1, Arg2, Val3)-angiotensin II in man

When des-(Asp¹, Arg², Val³)-angiotensin II was infused iv at rates of 308–5,550 pmol/kg·min for 10–120 min into 5 normal men and 2 patients with Bartter's syndrome, no significant change was observed in blood pressure (BP), plasma renin activity (PRA) or plasma aldosterone (PA), and the lowest dose did not inhibit a captopril-induced increase in PRA in the normal men, although des-(Asp¹, Arg²)-angiotensin II was reported in the same 5 normal men to cause a decrease in PRA and an increase in PA in this dose range and a rise in BP at 2,220 and 5,550 pmol/kg·min. However, an iv infusion of the pentapeptide at 9,000 pmol/kg·min for 15 min significantly raised BP in the 5 normal men but not in patients with Bartter's syndrome. BP returned to the pretreatment level 60 min after the cessation of the infusion, although the duration of the pressor actions of angiotensin II, angiotensin III and des-(Asp¹, Arg²)-angiotensin II were reported to be within 5 min in man. At the same dose level none of the 7 examined subjects showed any significant change in PRA or PA. Des-(Asp¹, Arg², Val³, Tyr⁴)-angiotensin II was infused iv at a rate of 41,480 pmol/kg·min into one of the normal men, but it caused no significant change in BP, PRA or PA. These results suggest that the pentapeptide and probably the tetrapeptide do not possess renin-suppressing and steroidogenic actions in man but the pentapeptide does elecit a minimal pressor action with a prolonged duration.     

Oxidant-induced pHi/Ca2+ changes in rat aortic smooth muscle cells: The role of atrial natriuretic peptide

The aim of this study was to investigate the effects of oxidative stress on PLD activity, [Ca²⁺]_i and pHi levels and the possible relationship among them. Moreover, since atrial natriuretic peptide (ANP) protects against oxidant-induced injury, we investigated the potential protective role of the hormone in Rat Aortic Smooth Muscle (RASM) cells exposed to oxidative stress. Water-soluble 2,2-Azobis (2hyphen;amidinopropane) dihydrochloride (AAPH) was used as free radical generating system, since it generates peroxyl radicals with defined reaction and the half time of peroxyl radicals is longer than other ROS. A significant increase of PLD activity was related to a significant decrease in pHi, while [Ca²⁺]_i levels showed an increase followed by a decrease after cell exposure to AAPH. [Ca²⁺]_i changes and pHi fall induced by AAPH were prevented by cadmium which inhibits a plasma membrane Ca²⁺ ATPase coupled to Ca²⁺/H⁺ exchanger, that operates the efflux of Ca²⁺ coupled to H⁺ influx. The involvement of PLD in pHi and [Ca²⁺]_i changes was confirmed by calphostin-c treatment, a potent inhibitor of PLD, which abolished all AAPH-induced effects. Pretreatment of RASM cells with pharmacological concentrations of ANP attenuated the AAPH effects on PLD activity as well as [Ca²⁺]_i and pHi changes, while no effects were observed with physiological ANP concentrations, suggesting a possible role of the hormone as defensive effector against early events of the oxidative stress.