Renal angiotensin II concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension

Renal immune cell infiltration and cells expressing angiotensin II (AII) in tubulointerstitial areas of the kidney are features of experimental models of salt-sensitive hypertension (SSHTN). A high-salt intake tends to suppress circulating AII levels, but intrarenal concentrations of AII have not been investigated in SSHTN. This study explored the relationship between these features to gain insight into the pathophysiology of SSHTN. Plasma angiotensin II (AII) and renal interstitial AII (microdialysis technique) and the infiltration of macrophages, lymphocytes, and AII-positive cells were determined in SSHTN induced by 5 wk of a high-salt diet (HSD) after short-term infusion of AII in rats with (n = 10) and without (n = 11) treatment with mycophenolate mofetil (MMF) and in control rats fed a high- (n = 7) and normal (n = 11) salt diet. As in previous studies, MMF did not affect AII-associated hypertension but reduced the interstitial inflammation and the SSHTN in the post-AII-period. During the HSD period, the AII group untreated with MMF had mean +/- SD) low plasma (2.4 +/- 1.4 pg/ml) and high interstitial AII concentration (1,310 +/- 208 pg/ml); MMF treatment resulted in a significantly lower interstitial AII (454 +/- 128 pg/ml). Renal AII concentration and the number of tubulointerstitial AII-positive cells were correlated. Blood pressure correlated positively with interstitial AII and negatively with plasma AII, thus giving compelling evidence of the paramount role of the AII within the kidney in the AII-induced model of salt-driven hypertension.     

Activation of subfornical organ efferents stimulates oxytocin secretion in the rat

The effects of activation of subfornical organ (SFO) efferents on plasma oxytocin concentrations were examined in conscious freely moving male Sprague-Dawley rats. Blood samples were obtained through chronically implanted atrial catheters and SFO efferents were activated electrically using chronically implanted bipolar stimulating electrodes. Hormone concentrations were measured by radioimmunoassay, and experimental animals were assigned to one of 3 experimental groups according to histologically verified anatomical locations of stimulating electrodes in either the SFO, the hippocampal commissure (HC), or the medial septum (MS). Electrical stimulation in the SFO resulted in increased plasma concentrations of oxytocin from control values of 2.54 +/- 0.9 pg/ml, to a post-stimulation level of 65.6 +/- 27.0 pg/ml. In contrast, stimulation in immediately adjacent structures including HC and MS was found to be without effect on plasma concentrations of oxytocin. These studies provide the first definitive evidence that SFO efferents may play a significant role in controlling the secretion of oxytocin from the posterior pituitary.     

Insulinhypoglycemia but not arginine infusion stimulates circulating plasma growth hormone-releasing hormone (GHRH) concentrations in children

The effect of insulinhypoglycemia and arginine infusion on circulating concentrations of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) has been studied in 24 children (4.4 to 14.3 years). Plasma GH and GHRH concentrations were determined by RIA. Basal plasma GHRH levels were detectable in the plasma of all patients ranging from 6.8 to 27.1 pg/ml. Injection of 0.1 U/kg body wt. insulin i.v. resulted in an increase of plasma GHRH levels (11.1 +/- 1.4 pg/ml vs. 18.8 +/- 2.6 pg/ml; P less than 0.01) preceding that of plasma GH (1.5 +/- 0.4 ng/ml vs. 13.6 +/- 1.3 ng/ml; P less than 0.01). Infusion of 0.5 gm/kg body wt. arginine hydrochloride did increase GH concentrations (2.0 +/- 0.6 ng/ml vs. 13.9 +/- 2.3 ng/ml; P less than 0.01) but did not change circulating plasma GHRH levels. Since the source of peripheral GHRH concentrations is not known the importance of these findings remains to be determined.     

The effect of angiotensin II and ADH on the secretion of atrial natriuretic factor

Studies in intact animals have suggested that angiotensin II (AII) and antidiuretic hormone (ADH) increase the plasma concentration of atrial natriuretic factor (ANF). The purpose of these studies was to examine the effects of AII and ADH on ANF secretion in a rat heart-lung preparation under conditions where aortic pressure could be regulated and other indirect effects of these hormones eliminated. ANF secretion was estimated as the total amount of ANF present in a perfusion reservoir at the end of each 30-min period. A pump was used to deliver a fluorocarbon perfusate to the right atrium at rates of either 2 or 5 ml/min. In a time control series where venous return was maintained at 2 ml/min for three 30-min periods ANF secretion was 672 +/- 114, 794 +/- 91, and 793 +/- 125 pg/min (n = 6, P greater than 0.05). When venous return was increased from 2 to 5 ml/min ANF secretion increased from 669 +/- 81 to 1089 +/- 127 pg/min (P less than 0.01). The addition of AII to the perfusate in concentrations of 50, 100, or 200 pg/ml (n = 6 in each group) had no significant effect on basal ANF secretion or the ANF response to increasing venous return. Similarly, the addition of ADH to the perfusate in concentrations of 5, 25, or 100 pg/ml had no significant effect on ANF release from the heart. These results suggest that the ability of AII and ADH to increase plasma ANF concentration in vivo may be due to the effects of these hormones on right or left atrial pressure.     

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.     

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.     

Plasma somatostatin in normal subjects and in various diseases: increased levels in somatostatin-producing tumors

The plasma levels of somatostatin (SRIF) were studied in normal subjects and patients with various disorders by a sensitive and specific radioimmunoassay. In 45 normal subjects, the fasting plasma SRIF concentrations were 13.3 +/- 5.3 pg/ml (mean +/- SD). Very high concentrations of plasma SRIF, ranging from 125.0 pg/ml to 400.0 pg/ml, were found in all four patients with medullary carcinoma of the thyroid examined and the SRIF levels were changed in parallel with their clinical course after resection of the tumor. A case of pheochromocytoma also showed a relatively high SRIF concentration in plasma (47.0 pg/ml), but the plasma SRIF level decreased to 8.7 pg/ml after removal of the tumor. In normal subjects, plasma SRIF levels did not fluctuate during 2 hr-observation period in basal state. Glucagon (1 mg, iv) and secretin (3 CHRU/kg B.W., iv infusion over 30 min) had no effect on the SRIF levels in the peripheral blood plasma of normal subjects. On intravenous infusion of arginine (0.5 g/kg B.W.) over 30 min, all 6 normal subjects showed a significant increase in plasma SRIF 30-45 min after the start of the infusion (basal value, 11.6 +/- 1.5 pg/ml; peak value, 27.2 +/- 3.0 pg/ml; p less than 0.005). Two cases of medullary thyroid carcinoma showed exaggerated responses after the arginine administration (increases of 103 pg/ml and 157 pg/ml, respectively), suggesting that SRIF was released from the tumor. The findings indicate that plasma SRIF determination in the basal state and after arginine administration is useful for detecting and following up SRIF-producing tumors.     

Aminopropionic acid receptors in paraventricular nucleus mediate pressor and vasopressin responses to endothelin-1 in subfornical organ

Endothelin-1 (ET-1) acts at selected brain loci to elicit a pressor response and secretion of vasopressin (AVP). Glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype mediate ET-1-induced AVP secretion in vitro, but the role of glutamatergic receptors in the pressor response and the secretion of AVP in vivo has not been studied. We hypothesized that both the pressor response and AVP secretion in response to ET-1 microinjection into subfornical organ (SFO) would be suppressed by ionotropic glutamatergic receptor antagonists in the paraventricular nucleus (PVN). Sinoaortic denervated male Long Evans rats were equipped with intracerebral cannulae directed into the SFO and the magnocellular region of the PVN bilaterally. Experiments were performed 5 days later in conscious rats. Direct injection of 5 pmol ET-1 into the SFO resulted in a 20 +/- 3 mm Hg increase in mean arterial pressure (MAP) (+/- SE) and a 14.1 +/- 0.3 pg/ml increase in the mean plasma AVP level (+/- SE) (P < 0.001 vs. artificial CSF) that was blocked by selective ET(A) inhibition. Neither the pressor response nor the increase in plasma AVP in response to ET-1 was altered despite prior injection of the NMDA blocker diclozipine (5 microg, MK801) into PVN bilaterally. In contrast, bilateral PVN injection with 6-cyano-7-nitroquinoxaline-2,3-dione (40 nmol, CNQX) prevented the pressor response (MAP +/- SE, - 4 +/- 4 mm Hg) and also inhibited AVP secretion (mean AVP level +/- SE, 0.16 +/- 0.50 pg/ml) (P < 0.001 vs. vehicle in PVN after injection of ET-1 into SFO). These findings support the conclusion that both the pressor response and AVP secretion in response to ET-1 acting at the SFO are mediated by a non-NMDA, most likely an aminopropionic acid glutamatergic receptor within the PVN.     

Possible involvement of endogenous beta-endorphin in the pathophysiological mechanisms of Pichinde virus-infected guinea pigs.

Previously, we demonstrated that naloxone, an opiate antagonist, prolonged survival of strain 13 guinea pigs infected with Pichinde virus. Thus, endogenous opiates may be involved in the pathogenesis of this viral disease. To determine whether endogenous opiate levels were affected by Pichinde viral infection, beta-endorphin concentrations in plasma and cerebrospinal fluid (CSF) of normal and infected strain 13 guinea pigs were measured by radioimmunoassay. Cerebrospinal fluid beta-endorphin concentrations were 78.0 +/- 13.2 pg/ml on postinoculation day (PID) 7, 59.0 +/- 5.6 pg/ml on PID 12, and 58.8 +/- 5.4 pg/ml on PID 14. These values were significantly higher than baseline levels of CSF beta-endorphin: 30.8 +/- 1.9 pg/ml. Plasma beta-endorphin concentrations of infected animals increased significantly to 202.1 +/- 17.9 pg/ml on PID 7 and to 154.2 +/- 21.4 pg/ml on PID 12 from a mean baseline value of 84.2 +/- 13.1 pg/ml. After a primer intravenous injection of beta-endorphin (10, 15, or 30 micrograms/kg), followed by constant infusion of beta-endorphin (15, 45, or 90 micrograms/kg.hr) to control noninfected guinea pigs, heart rate (except with the lowest dose) and mean blood pressure decreased markedly. Under these experimental conditions, concentrations of plasma and CSF beta-endorphin increased simultaneously with different magnitude. Because both Pichinde viral infection and beta-endorphin administration produced a similar trend of cardiovascular disturbances, leading to hypotension and bradycardia, increased concentrations of plasma and CSF beta-endorphin may play a partial role in the pathophysiological mechanisms of Pichinde virus infection.     

Role of angiotensin II and vasopressin in cisplatin-induced emesis

Cisplatin-containing chemotherapy regimens are known to produce intense nausea and vomiting. Angiotensin II (AII) and vasopressin (AVP) have been shown to have emetic properties. The role of these two peptides on cisplatin-induced vomiting was investigated in beagle dogs. Cisplatin (2 mg/kg, IV over 5 min) produced consistent emesis in all dogs after a mean latency time of 144 +/- 4 min. Serum Angiotensin Converting Enzyme (ACE) and plasma AII levels did not significantly change 3 hr after cisplatin administration (at the time of nausea and emesis) in control animals. AVP levels rose from 0.3 pg/ml to 7.5 pg/ml 3 hrs after cisplatin. Complete inhibition of ACE with enalapril (given at 3 mg/kg p.o., 3 hrs prior to cisplatin) reduced AII levels by 70%, but failed to significantly modify the increase in AVP levels (7.2 +/- 2.2 pg/ml), the latency time to emesis (149 +/- 2 min) and the number of emetic episodes induced by cisplatin. These results suggest that AII does not mediate cisplatin-induced emesis, nor does it mediate the increase in AVP observed at the time of emesis. We propose that AVP may be a good marker for nausea and emesis, and that increases in AVP may be neurally-mediated. The large increase in circulating AVP may represent a desirable water conservation response in anticipation of fluid losses induced by vomiting.     

Chlorpropamide-ethanol induced met-enkephalin secretion in dogs: release mechanisms and biochemical characterisation

Circulating met-enkephalin-like immunoreactivity (MLI) rises in man after chlorpropamide and ethanol although the origin and molecular forms of circulating MLI are not well defined. We have studied the response to oral ethanol in conscious and anaesthetised dogs pretreated with chlorpropamide. In conscious dogs MLI rose from a basal level of 29 +/- 7 pg/ml to a peak of 55 +/- 14 pg/ml 10 min after ethanol (P less than 0.001). In anaesthetised animals, following ethanol, plasma MLI rose in caval (35 +/- 6 pg/ml to a peak of 70 +/- 10 pg/ml), in portal (28 +/- 6 pg/ml to 51 +/- 6 pg/ml) and in adrenal blood (897 +/- 316 pg/ml to 1483 +/- 298 pg/ml; P less than 0.001). Biogel P-4 chromatography of caval and portal basal plasma showed 87% of MLI measured coeluted with the synthetic pentapeptide, while chromatography of peak plasma showed that only 65% coeluted with the pentapeptide and the remaining 35% was of larger molecular size. Sephadex G75 chromatography of adrenal vein plasma revealed three peaks of MLI of differing molecular sizes (8 k = 69.7%; 3-5 k = 12.1% and the pentapeptide = 18.2%). Treatment of the column fractions with trypsin and carboxypeptidase B resulted in the generation of new MLI with peaks of approximate molecular sizes 31 k (10.4%), and 18 k (37.1%) in addition to 8 k (40.0%), 3-5 k (5.0%) and the pentapeptide (7.5%). Acetaldehyde involvement in MLI release was investigated. Following acetaldehyde infusion, plasma MLI rose both in caval (35 +/- 9 pg/ml to 86 +/- 8 pg/ml) and adrenal vein (417 +/- 121 pg/ml to 1768 +/- 433 pg/ml) bloods. Thus we have established an animal model which enables further study of the mechanisms of MLI release and characterisation of the molecular forms. The adrenal medulla, unlike the gut, may be an important source of circulating met-enkephalin and acetaldehyde formation an essential intrinsic component of chlorpropamide-ethanol induced met-enkephalin release.     

Secretory protein 7B2. A novel tumor marker of medullary carcinoma of the thyroid

Mean plasma concentrations of 7B2 in three patients with medullary carcinoma of the thyroid (MCT) (294 +/- 38 pg/ml) were significantly higher than those in age-matched normal subjects (107.2 +/- 7.2 pg/ml, n = 11). The intravenous infusions of pentagastrin (0.5 microgram/kg) markedly increased the plasma concentrations of 7B2 as well as calcitonin in all three MCT patients but it caused no significant rise of the plasma 7B2 concentration in any healthy subjects. The peak times and rates of increase of plasma 7B2 concentrations were different from those of plasma calcitonin concentrations in MCT patients. The plasma 7B2 concentration in one of the patients with MCT showed a marked reduction and no further elevation from the pentagastrin infusion following a total thyroidectomy (preop. 226 pg/ml; postop. 112.1 pg/ml). The above evidence suggests that the increased levels of plasma 7B2 in MCT patients may be attributed to the release from parafollicular cells of thyroid. Therefore, 7B2 is considered to be clinically useful as a tumor marker of MCT.     

Plasma catecholamine concentrations of newborn piglets in thermoneutral and cold environments

Plasma epinephrine and norepinephrine concentrations were measured in seventeen unanaesthetized 3 to 4 days-old piglets while in a thermoneutral environment (31.3 degrees C) and 30, 45 and 60 min after induction of environmental cold stress (19.9-23.1 degrees C). Plasma epinephrine and norepinephrine concentrations in a warm environment were 142 +/- 26 pg/ml, and 456 +/- 44 pg/ml respectively. Environmental cold stress evoked significant increases in norepinephrine values after 30 (624 +/- 58 pg/ml), 45 (626 +/- 60 pg/ml) and 60 (626 +/- 54 pg/ml) min of cold stress. Plasma epinephrine concentrations did not significantly change during environmental cold stress. Post-hoc stratification of piglets into normothermic (deep rectal temperature 38.6 degrees C-38.8 degrees C, n = 9) and hypothermic (deep rectal temperature 37.1 degrees C-37.7 degrees C, n = 7) subgroups revealed significant increases in plasma norepinephrine concentrations only in the hypothermic subgroup. We conclude that plasma norepinephrine, but not epinephrine, is increased in newborn piglets during environmental cold stress and that the changes in norepinephrine concentrations are related to body core hypothermia. We speculate that hypothermia-mediated reductions in peripheral norepinephrine breakdown and re-uptake contribute to the rise in circulating levels.     

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.     

Decreased vascular reactivity to norepinephrine in Fischer rats with neoplasia-induced hypercalcemia

The effect of a hypercalcemia-producing Leydig cell tumor on vascular reactivity in Fischer rats was studied. Seven to eight days after tumor implantation, there was no difference between tumor (T) and control (C) animals in serum calcium, serum phosphate, plasma catecholamine levels, mean arterial pressure (MAP), or blood pressure responses to norepinephrine (NE) infusion. At day 12-13 of tumor growth, the serum calcium in the tumor-bearing rats was significantly higher (12.2 +/- 0.8 vs. 9.7 +/- 0.3 mg%, P less than .01) and their serum phosphate significantly lower (4.5 +/- 0.3 vs. 5.7 +/- 0.4 mg%, P less than .01) than controls. Plasma epinephrine (E) (497 +/- 154 vs. 62 +/- 13 pg/ml, P less than .05), and norepinephrine (NE) (686 +/- 85 vs. 329 +/- 75 pg/ml, P less than .01) were markedly elevated in the tumor rats. MAP and the blood pressure responses to graded NE infusions were significantly lower in tumor animals at Day 12-13, whereas there was no change in sensitivity to angiotensin II (AII) infusions. In vitro contractile responses of tail artery segments to transmural nerve stimulation (TNS) in animals with tumors were lower than in controls but there were no differences in sensitivity to exogenous NE in vitro. These results suggest that the tumor stimulates production of a circulating factor which desensitizes NE receptors and that this tumor also decreases neurovascular function by an undefined mechanism.     

Endothelin-3 concentrations in human plasma: the increased concentrations in patients undergoing haemodialysis

Plasma immunoreactive endothelin-3 (ir-ET-3) concentrations were measured by a sandwich-enzyme immunoassay (sandwich-EIA) for endothelin-3 (ET-3). The assay method consists of two antibodies directed against N-terminal and C-terminal portions of ET-3. It detects as little as 0.1 pg/well of ET-3 without the crossreaction with endothelin-1, endothelin-2 and big ET-3. Plasma ir-ET-3 concentrations were found to be 0.45 +/- 0.07 pg/ml (mean +/- SD) in healthy volunteers, and were increased in patients undergoing haemodialysis (0.83 +/- 0.26 pg/ml, p less than 0.001). In reverse-phase HPLC, ir-ET-3 in normal plasma and in plasma of haemodialysis patients was eluted at the position of authentic ET-3, indicating that ir-ET-3 in plasma detected by the EIA was ET-3 itself. These results suggest that circulating ET-3 exists in normal human plasma and that production and/or metabolism of ET-3 may be altered in patients undergoing haemodialysis.     

Catecholamine response is attenuated during moderate-intensity exercise in response to the "lactate clamp"

Catecholamine release is known to be regulated by feedforward and feedback mechanisms. Norepinephrine (NE) and epinephrine (Epi) concentrations rise in response to stresses, such as exercise, that challenge blood glucose homeostasis. The purpose of this study was to assess the hypothesis that the lactate anion is involved in feedback control of catecholamine concentration. Six healthy active men (26 +/- 2 yr, 82 +/- 2 kg, 50.7 +/- 2.1 ml.kg(-1).min(-1)) were studied on five occasions after an overnight fast. Plasma concentrations of NE and Epi were determined during 90 min of rest and 90 min of exercise at 55% of peak O2 consumption (VO2 peak) two times with exogenous lactate infusion (lactate clamp, LC) and two times without LC (CON). The blood lactate profile ( approximately 4 mM) of a preliminary trial at 65% VO2 peak (65%) was matched during the subsequent LC trials. In resting men, plasma NE concentration was not different between trials, but during exercise all conditions were different with 65% > CON > LC (65%: 2,115 +/- 166 pg/ml, CON: 1,573 +/- 153 pg/ml, LC: 930 +/- 174 pg/ml, P < 0.05). Plasma Epi concentrations at rest were different between conditions, with LC less than 65% and CON (65%: 68 +/- 9 pg/ml, CON: 59 +/- 7 pg/ml, LC: 38 +/- 10 pg/ml, P < 0.05). During exercise, Epi concentration showed the same trend (65%: 262 +/- 37 pg/ml, CON: 190 +/- 34 pg/ml, LC: 113.2 +/- 23 pg/ml, P < 0.05). In conclusion, lactate attenuates the catecholamine response during moderate-intensity exercise, likely by feedback inhibition.     

Estrogens and prostaglandin F2alpha in the semen and blood plasma of stallions

A study was performed to determine the levels of estrogens and prostaglandin F(2)alpha in the stallion ejaculate. Simultaneous semen and blood plasma samples were collected from 19 stallions, 2 weeks apart, during the breeding season. Although not statistically different, the total mean estrogen content tended to be higher in seminal plasma (4447 pg/ml) than in blood (2497 pg/ml). A tendency was found for higher mean estrone sulphate concentrations than for total free steroid in both seminal (4116.1 vs 330.5 pg/ml) and blood plasma (2447.1 vs 49.5 pm/ml). Mean concentrations of estrone in ejaculate and blood plasma were 257.1 +/- 267.0 (SD) and 9.5 +/- 5.4 pg/ml, respectively. Estradiol-17beta concentrations were 73.4 +/- 87.4 and 40.0 +/- 27.6 pg/ml in ejaculates and blood plasma, respectively. Mean PGF(2)alpha concentrations tended to be much higher than total estrogens (1106.8 +/- 1636.4, SD, vs approximately 260 ng/ejaculate, respectively). To our knowledge this is the first report of PGF(2)alpha and estrogen concentrations in the stallion ejaculate.     

Angiotensin II mediates hyperadrenergic activity evoked by sodium restriction in essential hypertension

We examined the possible involvement of angiotensin II in the modulation of circulating norepinephrine produced by acute sodium restriction in essential hypertensive patients (n = 18). Sodium restriction potentiated plasma level of norepinephrine in parallel with an increased plasma renin activity (r = 0.81, F = 31.2, p less than 0.05 given by the percent changes). An intravenous infusion of sarcosine-1, isoleucine-8 angiotensin II produced a significant fall in mean arterial pressure (-6 +/- 2 mmHg, p less than 0.05) in patients on sodium restriction but not before sodium restriction, while the infusion of the antagonist produced a greater decrease (p less than 0.05) in plasma norepinephrine with sodium restriction (-158 +/- 23 pg/ml, p less than 0.05) when compared to that obtained before sodium restriction (-91 +/- 11 pg/ml, p less than 0.05). A single oral administration of an angiotensin I converting enzyme inhibitor, captopril caused a greater fall (p less than 0.01) in mean arterial pressure after sodium restriction (-32 +/- 3 mmHg, p less than 0.05) compared to that given before (-21 +/- 3 mmHg, p less than 0.05). However, sodium restriction did not affect the magnitude of reflex increase in plasma norepinephrine to hypotension evoked by captopril (from +88 +/- 16 pg/ml to +87 +/- 17 pg/ml; p greater than 0.05). It can be interpreted that acute sodium depletion results in a substantial contribution of angiotensin II to the expression of hyperadrenergic activity.     

Plasma concentrations of endothelin in patients with abnormal vascular reactivity. Effects of ergometric exercise and acute saline loading

We measured circulating concentrations of endothelin, a recently discovered vasoconstrictor peptide produced by vascular endothelial cells, in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radio-immunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects (n = 20), in patients with diabetes mellitus type I (n = 10), in patients with mild to moderate essential hypertension (n = 12) and in non-dialyzed patients with stable chronic renal failure (n = 12). Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0 +/- 0.6 pg/ml, 4.7 +/- 0.2 pg/ml and 6.5 +/- 1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6 +/- 2.9 pg/ml (p less than 0.005). No correlations were observed between serum creatinine concentrations ranging from 124 to 850 mumol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin. Thus, it is unlikely that vascular synthesis of endothelin is related to acute physiological changes in systemic hemodynamics or to the circulatory and renal responses to acute extracellular fluid volume (ECFV) expansion. A potential role of endothelin, however, in the control of regional blood flow cannot be excluded. Elevated plasma concentrations of endothelin observed in patients with chronic renal failure require further investigations.