Effect of high calcium diet on the development of high blood pressure in intact spontaneously hypertensive rats and in adrenalectomized spontaneously hypertensive rats treated with aldosterone

The current investigation was designed to study the effect(s) of high calcium diet on the development of high blood pressure (BP) in both young intact spontaneously hypertensive rats (SHRs) and in young adrenalectomized (ADX) male SHRs treated with aldosterone (ALDO). Weaned SHRs were fed either a control calcium diet (0.5% Ca as PO4) (CCaDiet), a high calcium diet (2.5% Ca, 0.5% as PO4 and 2% as CO3) (HCaDiet), or Agway ProLab rat food containing 2.5% Ca (HCaPLDiet). The HCaDiet significantly blunted the development of high BP in young intact SHRs (P less than 0.001; n = 8 to 10). At 6 weeks of age, BP was 117 +/- 2 mm Hg (HCaDiet) compared with 135 +/- 3 mm Hg (CCaDiet); by 12.7 weeks of age, BP was 192 +/- 4 mm Hg (HCaDiet) compared with 233 +/- 3 mm Hg (CCaDiet). Similar results were observed in age-matched SHRs fed the HCaPLDiet. The results show that subcutaneous infusion of ALDO (1.0 microgram/d, osmotic pumps) for 2 weeks to young ADX male SHRs raised on the CCaDiet caused a significant increase in systolic BP when compared with SHRs implanted with Sham pumps (P less than 0.001). High BP associated with ALDO infusion was attenuated by the HCaDiet (BP after 2 weeks was 138 +/- 8 mm Hg for the HCaDiet group compared with 200 +/- 5 mm Hg for the CCaDiet group, P less than 0.001; n = 4 to 6). The results show that the HCaDiet blunts the development of high BP in intact SHRs and may protect against the development of ALDO hypertension in ADX young SHRs.     

Effect of naloxone on gonadotrophin secretion at various stages of development in the ewe lamb

Spring-born crossbred ewe lambs were raised in a natural photoperiod and saline (N = 6) or naloxone (1 mg/kg) in saline (N = 6) was injected (i.m.) every 2 h for 6 h at 5, 10 and 15 weeks of age and for 8 h at 20, 25 and 30 weeks of age. Blood samples were taken every 12 min during treatment periods. Naloxone had no effect on time to first oestrus (controls 235 +/- 6 days, naloxone 242 +/- 7 days). Mean serum LH concentrations and LH pulse frequency were elevated by naloxone in ewe lambs at 20, 25, and 30 weeks of age (P less than 0.05). The only FSH response to naloxone was a depression of mean serum concentrations at 30 weeks of age (P less than 0.05). LH pulse amplitude was elevated at 5 weeks of age in all ewe lambs and declined thereafter to a nadir at 30 weeks of age in control, but not in naloxone-treated animals (P less than 0.05). LH pulse frequency was elevated at 10 weeks of age in control ewe lambs and in all animals at 30 weeks of age (P less than 0.05). FSH pulse frequency declined from 5 weeks of age in control ewe lambs (P less than 0.05), with very few pulses noted in 25- and 30-week-old animals. We conclude that (1) opioidergic suppression of LH, but not FSH, secretion developed at 20 weeks of age in the growing ewe lambs used in the present study, with no obvious change in suppression before the onset of first oestrus: (2) pulsatile FSH secretion occurred in the young ewe lamb but was lost as the lamb matured: (3) attainment of sexual maturity was preceded by an elevation in LH pulse frequency.     

Maturational changes in opioidergic control of luteinizing hormone and follicle-stimulating hormone in ram lambs

Stimulation by naloxone, an opioid antagonist, of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion was examined in spring-born crossbred ram lambs raised under natural photoperiod. Vehicle (n = 6) or 1 mg naloxone/kg vehicle (n = 6) was injected (i.m.) 3 times at 2-h intervals at 5, 10 and 15 weeks of age and 4 times at 2-h intervals at 20, 25, 30 and 35 weeks of age. Blood samples were taken every 12 min for 6 h at 5, 10 and 15 weeks of age and for 8 h at 20, 25, 30 and 35 weeks of age. Naloxone had no effect on age at sexual maturity (controls 239 +/- 23 days; naloxone 232 +/- 33 days). The only significant (P less than 0.05) effect of naloxone on FSH was a greater pulse amplitude in 10-week-old treated lambs than in control lambs. Naloxone treatment resulted in greater LH pulse amplitude at 5 and 10 weeks of age (P less than 0.05), lower basal serum concentration of LH at 10 weeks of age (P less than 0.05), greater LH pulse frequency at 25 weeks of age (P less than 0.05), and greater mean serum concentrations of LH, basal LH and LH pulse amplitude at 35 weeks of age (P less than 0.01) than in the controls. In both groups of lambs, mean and basal FSH, and LH and FSH pulse amplitude were highest at 5 weeks of age and fell with age. LH pulse amplitude was lowest at 35 weeks of age (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylactic effects of magnesium and vitamin E in rat spinal cord radiation damage: evaluation based on lipid peroxidation levels

This study investigated the neuroprotective effects of magnesium sulfate prophylaxis and vitamin E prophylaxis in a rat model of spinal cord radiation injury. Groups were subjected to different treatment conditions for 5 days prior to irradiation, and outcomes were evaluated on the basis of lipid peroxidation levels in cord tissue. Four groups of rats were investigated: no radiation/treatment (n = 4), intraperitoneal (i.p.) saline 1 ml/day (n = 6), i.p. vitamin E 100 mg/kg/day (n = 6), and i.p. magnesium sulfate 600 mg/kg/day (n = 6). The thoracic cord of each non-control rat was exposed to 20 Gy radiation in a LINAC system using 6 MV x-rays, and malondialdehyde (MDA) levels (reflecting lipid peroxidation level) were determined 24 hours post-irradiation. The MDA levels in thoracic cord segments from the control rats were used to determine baseline lipid peroxidation. The mean levels in the control, saline-only, vitamin E, and magnesium sulfate groups were 12.12 +/- 0.63, 27.0 +/- 2.81, 17.71 +/- 0.44, and 14.40 +/- 0.47 nmol/mg tissue, respectively. The MDA levels in the saline-only group were significantly higher than baseline, and the levels in the vitamin E group were significantly lower than those in the saline group (P < 0.05 for both). The levels in the magnesium sulfate group were dramatically lower than those in the saline group (P < 0.001). The results indicate that i.p. magnesium sulfate has a marked neuroprotective effect against radiation-induced oxidative stress in the rat spinal cord.     

Photoperiodic variation of Leydig cell numbers in the testis of the golden hamster: a possible mechanism for their renewal during recrudescence

Golden hamster testes regress after short day exposure. The present study asks: 1) are Leydig cell numbers depleted during short days, and 2) if so, how are they replenished during recrudescence. Control hamsters were shown 14 h of light and 10 h of dark (LD 14:10) for 10 weeks (n = 12). Testicular regression was induced by LD 6:18 for 10 weeks (n = 4), and recrudescence by switching regressed hamsters to LD 14:10 for 3 and 5 weeks (n = 8 for each group). All hamsters were injected with [3H]thymidine [3 microCi/gm body wt., intraperitoneally (i.p.)] 1 h or 2 weeks before sacrifice. Leydig cell number per testis was determined by stereological analysis of sections of perfusion-fixed testes, and labeling indices were determined by autoradiography. Leydig cell numbers were reduced significantly from 18.2 X 10(6) in control to 9.0 X 10(6) in regressed testes (p less than 0.05); then increased to 14.0 X 10(6) and 17.9 X 10(6) in 3- and 5-week recrudesced hamsters. The labeling index was nondetectable (n.d.) for regressed hamsters. In control and recrudescing hamsters the labeling index was measured at two times (t1 = 1 h vs. t2 = 2 weeks post-injection): in controls, t1 = 0.22 +/- 0.15% (mean +/- SEM) vs. t2 = 0.28 +/- 0.22%; in 1 week recrudesced, n.d. vs. 1.92 +/- 0.77% (p less than 0.05); at 3 wk, n.d. vs. 4.58 +/- 1.74% (p less than 0.05); at 5 weeks, 1.92 +/- 0.61% vs. 2.25 +/- 0.59%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of treatment with LH or FSH from 4 to 8 weeks of age on the attainment of puberty in bull calves

A transient increase in gonadotropin secretion between 6 and 20 weeks of age is critical for the onset of puberty in bull calves. To try and hasten the onset of puberty, bull calves were treated (s.c.) with 3 mg of bLH (n = 6) or 4 mg of bFSH (n = 6) once every 2 days, from 4 to 8 weeks after birth; control calves received saline (n = 6). At 4 and 8 weeks of age, mean LH concentrations were higher (P < 0.05) in bLH-treated (2.3 +/- 0.04 ng/ml and 1.20 +/- 0.04 ng/ml) as compared to control calves (0.50 +/- 0.1 ng/ml and 0.70 +/- 0.10 ng/ml). Mean serum FSH concentrations at 4 and 8 weeks of age, were higher (P < 0.05) in bFSH-treated (1.60 +/- 0.20 ng/ml and 1.10 +/- 0.2 ng/ml) as compared to control calves (0.38 +/- 0.07 ng/ml and 0.35 +/- 0.07 ng/ml). The age at which scrotal circumference (SC) first reached > or = 28 cm, occurred earlier (P < 0.05) in bFSH-treated calves as compared to saline-treated calves (39.3 +/- 1.3 and 44.8 +/- 1.3 weeks of age, respectively). Based on testicular histology at 56 weeks of age, treatment with bFSH resulted in greater (P < 0.05) numbers of Sertoli cells (5 +/- 0.2, 6 +/- 0.3 and 5 +/- 0.3 in bLH-, bFSH- and saline-treated calves, respectively); elongated spermatids (42 +/- 2, 57 +/- 8 and 38 +/- 5 in bLH-, bFSH- and saline-treated calves, respectively) and spermatocytes (31 +/- 3, 38 +/- 3 and 29 +/- 2 in bLH-, bFSH- and saline-treated calves, respectively) per seminiferous tubule. We concluded that treatment of bull calves with bFSH from 4 to 8 weeks of age increased testicular growth (SC); hastened onset of puberty (SC > or = 28 cm); and enhanced spermatogenesis.     

Effect of intravaginal implants of melatonin on the onset of ovarian activity in adult and prepubertal ewes

Melatonin was administered intravaginally in Silastic tubing to adult and prepubertal ewes. In Exp. 1, ewe lambs (born early March) were given intravaginal melatonin implants at a mean age (+/- s.e.m.) of 7.5 +/- 0.1 weeks (Group E, N = 10) or 19.4 +/- 0.2 weeks (Group L, N = 10). The third group (Group C, N = 10) received empty implants. In Exp. 2 mature ewes were given implants on 13 May (Group E, N = 10) or 18 July (Group L, N = 10) or received empty implants (Group C, N = 10) on one of these two dates. Blood samples were taken twice weekly for progesterone assay. In Exp. 1 the mean age (+/- s.e.m.) at puberty (progesterone greater than 2 nmol/l for two consecutive samples) was 35.4 +/- 0.8 weeks. Puberty was advanced by 5.2 weeks in Group L lambs, occurring at a mean age of 30.2 +/- 0.7 weeks (P less than 0.001). In Group E lambs the timing of puberty was unaltered, occurring at a mean age of 34.8 +/- 0.6 weeks. Mature ewes in Group L (Exp. 2) showed increased incidence of ovarian activity (9/10 ewes cycling by 26 September) compared with the control ewes (1/10) (P less than 0.001), but there was no effect in Group E ewes (3/10). The results demonstrate that continuous melatonin administration to adult and prepubertal ewes can mimic the effect of short days in terms of the reproductive response, and that the present and previous exposure to melatonin is critical in determining the response.     

Physiological changes in androgen plasma levels with elapsing of time from castration in adult male rats

In the present study we investigated in adult male rats the effects of castration on Dehydroepiandrosterone (DHEA), Androstenedione (delta 4), Testosterone (T) and Dihydrotestosterone (DHT) plasma levels: five days (group II), seven weeks (group III) and eleven weeks (group IV) after orchiectomy. The same hormone assays were performed in rats approximately 60 days of age which underwent a sham-operation for orchiectomy (group I). Our data show that five days following orchiectomy (group II) delta 4, T and DHT were decreased with respect to sham-operated rats. (Group I: delta 4: 83.3 +/- 14.9 (SEM) ng/dl (n = 12); T: 435.32 +/- 51.45 (n = 12); DHT: 51.47 +/- 6.54 (n = 12); Group II: delta 4: 44.81 +/- 6.09 (n = 12) P = 0.05; T: 25.54 +/- 2.88 (n = 12) P less than 0.01; DHT: 12.9 +/- 2.51 (n = 12) P less than 0.01). Seven weeks afterwards T and DHT remained significantly lower (group III: T: 54.37 +/- 12.21, n = 16) (P less than 0.01; DHT: 33.22 +/- 4.49 (n = 16) P less than 0.01) while eleven weeks after all steroids were significantly decreased with respect to the values observed in sham-operated rats. (Group IV) delta 4: 32.01 +/- 5.7 (n = 10) P less than 0.01: T: 27.29 +/- 7.05 (n = 10) P less than 0.01; DHT: 29.03: 5.34 (n = 10) P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor in liver cirrhosis--the influence of volume expansion

Plasma levels of atrial natriuretic factor (ANP) were examined in 12 patients with liver cirrhosis (6 with ascites) and 6 controls before and after the administration of the infusion of 2000 ml of saline solution per 70 kg of body weight during 2 hours. Basal concentration of ANF tended to be slightly, but nonsignificantly higher in patients with ascitic liver cirrhosis (5.5 +/- 1.3 fmol/ml) than in controls (3.0 +/- 1.0 fmol/ml) and in patients with non-ascitic liver cirrhosis (4.6 +/- 1.3 fmol/ml). Saline administration led to the comparable increase of plasma ANF in ascitic (14.2 +/- 4.0 fmol/ml) and non-ascitic cirrhotics (15.7 +/- 3.7 fmol/ml) and in controls (12.4 +/- 4.3 fmol/ml). The increase of plasma ANF was accompanied by the suppression of plasma renin activity (PRA) and plasma aldosterone (PA) in all groups; in ascitic patients, however, PRA and PA remained above the normal range. While in controls and non-ascitic cirrhotics saline administration led to the increase of urine flow rate /from 0.74 +/- 0.13 to 2.04 +/- 0.44 ml/min, P less than 0.01, in controls; from 0.83 +/- 0.05 to 1.28 +/- 0.07 ml/min, P less than 0.01, in non-ascitic cirrhotics) and urinary sodium excretion (from 110.7 +/- 21.3 to 364.8 +/- 74.4 umol/min, P less than 0.01, in controls; from 125.0 +/- 16.7 to 218.7 +/- 24.3 umol/min, P less than 0.01 in non-ascitic cirrhotics), in patients with ascitic liver cirrhosis neither urine flow rate (from 0.66 +/- 0.1 to 0.72 +/- 0.15 ml/min, n.s.), nor urinary sodium excretion (from 16.7 +/- 9.9 to 54.2 +/- 40.3 umol/min, n.s.) changed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs.

The efficacy of human extracellular-superoxide dismutase type C (EC-SOD C) to limit infarct size after ischemia and reperfusion was explored and compared to that of EC-SOD C combined with catalase (CAT) and to that of CAT alone. EC-SOD C binds to heparan sulphate proteoglycan on the cell surfaces. Thirty-two pigs were subjected to 45 min of myocardial ischemia followed by 4 h of reperfusion. Control pigs (group A; n = 8) received 300 mL of saline into the great cardiac vein during a 30-min period started 5 min prior to reperfusion; pigs in group B (EC-SOD C; n = 8) got 16.6 mg of EC-SOD C; pigs in group C (EC-SOD C + CAT; n = 8) got 16.6 mg of EC-SOD C together with 150 mg of CAT. Pigs in group D (CAT; n = 8) received 150 mg of CAT. In groups B, C, and D, the drug was dissolved in saline and infused into the great cardiac. Infarct size expressed as percent of area at risk was smaller in groups B (14.5 +/- 16.7%) and C (40.8 +/- 13.3%) than in groups A (78.8 +/- 8.6%) and D (67.2 +/- 18.6%; p less than .05). Creatine kinase (CK) activity in ischemic myocardium was higher in groups B (1740 +/- 548 U/g) and C (1729 +/- 358 U/g) than in groups A (1184 +/- 237 U/g) and D (1251 +/- 434 U/g; p less than .05). There was an inverse relation (r = -.83) between infarct size and CK content. The EC-SOD C infusions resulted in only minimal increases in plasma SOD activities. In conclusion, the presence of SOD on the cell surfaces is of importance in the prevention of reperfusion injury rather than circulating SOD.     

Attenuation of the development of hypertension in spontaneously hypertensive rats by the thromboxane synthetase inhibitor, 4'-(imidazol-1-yl) acetophenone

The compound 4'-(imidazol-1-yl) acetophenone was demonstrated to be a selective thromboxane (Tx) synthetase inhibitor in spontaneously hypertensive rats (SHR). Serum TxB2 concentrations (from clotted blood) were suppressed by 89.1% (p less than 0.001) and 41.2% (p less than 0.01) at 3 and 24 hours, respectively, following a single subcutaneous injection of 100 mg/kg of 4'-(Imidazol-1-yl) acetophenone suspended in olive oil. In contrast, plasma 6-keto-PGF1 alpha levels were not significantly altered at 3 hours following injection - a time when suppression of TXB2 was maximal. From 4 to 10 weeks of age, SHR were treated with daily injections of either 4'-(Imidazol-1-yl) acetophenone (100 mg/kg) in olive oil or olive oil alone. By 8 weeks of age systolic blood pressures in the treated group were 140.6 +/- 3.2 vs 156.6 +/- 4.5 mmHg in the control group (p less than 0.01). At ten weeks of age the separation was even more pronounced: 155.3 +/- 3.7 vs. 184.8 +/- 4.6 mmHg for treated vs. control animals (p less than 0.001). This data supports the hypothesis that thromboxanes may be involved in the development of SHR hypertension; however, alternative mechanisms are discussed.     

Oxidative stress in very low birth weight infants as measured by urinary 8-OHdG

Very low birth weight (VLBW) infants can be subjected to oxidative stress in the course of intensive care. We measured 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative stress, and estimated the degree of oxidative stress in such infants. We also examined if the administered oxygen was related to oxidative stress. Urine samples of 50 Japanese VLBW infants [birth weights: 956.3+/-277.6g, and gestational ages: 28.0+/-2.6 weeks (mean +/- SD)] were collected on various postnatal days and 8-OHdG levels were determined using an ELISA kit. Sixteen term infants served as normal controls. As body weights at sampling increased, the average levels of urinary 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants under 1000g, 29.5+/-16.4 micromol/mol creatinine (n = 24); 1000-1500g, 23.8+/-14.9 (n = 12); over 1500g, 16.1+/-8.5 (n = 14); and control, 10.9+/-7.2 (n = 16). Significant differences were found between <1000g group and > or = 1500g group (p = 0.0030), <1000g group and control (p < 0.0001), and 1000-1500g group and control (p = 0.0108). Also as postconceptional age at sampling increased, the average levels of 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants before 252 days (36 weeks) of postconception: 27.4+/-15.5 micromol/mol creatinine (n = 34); after 252 days, 18.2+/-12.5 (n = 16). Differences between <252 days group and control (p < 0.0001), and <252 days group and > or = 252 days groups (p = 0.0253) were statistically significant. Among the three groups based on ambient oxygen concentration (21%, 22-29%, and > or = 30%) there was no significant difference (p = 0.417). The more premature the infants were, the more intense was the oxidative stress, hence, it is the prematurity rather than the administered oxygen which causes oxidative stress in VLBW infants. Drury et al. ["Urinary 8-hydroxydeoxyguanosine in infants and children" Free Radic. Res. 28 (1998) 423-4281 measured urinary 8-OHdG of 28 infants (24-40 weeks gestation) and found no gestation or birthweight related differences. This discrepancy seemed to be because of difference in birth weights and sampling period of the subjects.     

Increased release of atrial natriuretic polypeptides in rats with DOCA-salt hypertension

This study compared atrial and plasma concentrations of immunoreactive alpha-rat atrial natriuretic polypeptide (i alpha-rANP) in rats given tap water (control), a 1% saline solution (salt), deoxycorticosterone acetate (DOCA) and DOCA plus 1% saline solution (DOCA-salt) after 1 and 8 weeks of treatment. DOCA (100 mg/kg) was given by implanting a piece of silicon rubber impregnated with DOCA subcutaneously. Atrial i alpha-rANP increased, while plasma i alpha-rANP decreased with time in all groups. Atrial concentration of i alpha-rANP was significantly lower in the DOCA-salt group than in the other groups at 1 week, and was reduced in the DOCA and DOCA-salt groups as compared to the control group at 8 weeks. On the other hand, plasma concentration of i alpha-rANP was significantly higher in the DOCA and the DOCA-salt groups than in the control group at 1 week; the DOCA and DOCA-salt group values were also higher than the control and salt group values at 8 weeks. Atrial concentration of i alpha-rANP was inversely correlated with systolic blood pressure in the all rats at 1 week (r = 0.48, p less than 0.001) and at 8 weeks (r = 0.33, p less than 0.05). Plasma concentration of i alpha-rANP was positively correlated with systolic blood pressure at 8 weeks (r = 0.37, p less than 0.05). In addition, there was a significant positive correlation between plasma/atrial ratio of i alpha-rANP concentration and systolic blood pressure at either stage (r = 0.41, p less than 0.01 at 1 week; r = 0.40, p less than 0.01 at 8 weeks). Thus, it seems likely that the release of ANPs is increased in response to expansion of extracellular fluid volume or elevation of blood pressure, modifying the development of hypertension in DOCA-salt rats.     

Changing responsiveness to growth hormone releasing factor in the perinatal sheep

Synthetic human pancreatic growth hormone releasing factor 1-44-amide was administered (8 micrograms/kg iv bolus) to chronically catheterised fetal sheep between 77 and 135 days of gestation and to infant sheep. At all ages human pancreatic growth hormone releasing factor induced a significant growth hormone response. In fetuses less than 120 days the integrated growth hormone response to human pancreatic growth hormone releasing factor (n = 5) was 250 +/- (SE) 50 ng X hr X ml-1 compared (p less than 0.001) to -22.8 +/- 8.6 ng X hr X ml-1 in saline treated controls (n = 7). In fetuses older than 120 days (n = 5), the response to human pancreatic growth hormone releasing factor was 110.8 +/- 15.6 ng X hr X ml-1 compared to -12.0 +/- 17.6 ng X hr X ml-1 in saline treated controls (n = 4 p less than 0.001). In 4 infant lambs (4-12 days) the response to human pancreatic growth hormone releasing factor (56.5 +/- 14.5 ng X hr X ml-1) was greater than in 6 control injected lambs (0.95 +/- 1.5 ng X hr X ml-1). The magnitude of the response to growth releasing factor decreased progressively with increasing postconceptual age (r = -0.80, p less than 0.001). These observations demonstrate that the fetal somatotrope can respond to exogenous growth releasing factor from at least 77 days of gestation. The progressive decrease in responsiveness may reflect the gradual development of somatostatin mediated inhibitory control or altered responsiveness of the somatotrope.     

Effects of atrial appendectomy on circulating atrial natriuretic factor during volume expansion in the rat

This study examined the changes in the circulating level of endogenous atrial natriuretic factor during diuresis and natriuresis produced by acute volume expansion in anesthetized rats with either bilateral atrial appendectomy (n = 9) or sham operation (n = 9). Following control measurements in the sham-operated rats, 1% body weight volume expansion with isotonic saline produced an increment in urinary sodium excretion of over 4 mueq/min (P less than 0.05) while urine volume increased by more than 20 microliter/min (P less than 0.05). These responses were associated with a significant increase in immunoreactive plasma atrial natriuretic factor from a baseline value of 82 +/- 10 pg/ml to a level of 120 +/- 14 pg/ml (P less than 0.05). In contrast, in the group of rats with bilateral atrial appendectomy an identical degree of volume expansion increased urinary sodium excretion and urine volume by only 0.61 mueq/min (P less than 0.05) and 3.07 microliter/min (P less than 0.05), respectively. In this group, immunoreactive plasma atrial natriuretic factor remained statistically unchanged from a control value of 70 +/- 12 pg/ml to a level of 82 +/- 16 pg/ml (P greater than 0.05). Comparison of the two groups indicates that the natriuresis, diuresis, and plasma atrial natriuretic factor levels during volume expansion were significantly reduced in the rats with bilateral atrial appendectomy. No differences in mean arterial pressure and heart rate were observed between the two groups. These data demonstrate that removal of both atrial appendages in the rat attenuated the release of atrial natriuretic factor during volume expansion; and this effect, in turn, was associated with a reduction in the natriuretic and diuretic responses.     

Effects of hyperoxia on alveolar permeability of neutropenic rabbits

We investigated whether neutrophil suppression would prevent the early hyperoxic injury to the rabbit alveolar epithelium. Rabbits received a single intravenous injection of either nitrogen mustard (2 mg/kg) or saline and were exposed to 100% C2 for 64 h. At the end of the hyperoxic exposure, there were 20 +/- 7 neutrophils/ml blood in the nitrogen mustard group vs. 5,935 +/- 1,174 in the control group (means +/- SE; P less than 0.05). The corresponding numbers in lung extravascular tissue, expressed per high-power field, were 0.37 +/- 7 and 5.9 +/- 0.35, respectively (P less than 0.05). At this time, the rate constants of solute flux for 57Co-vitamin B12 (r = 6.5 A) and 131I-cytochrome c (r = 17 A), across the alveolar epithelium, were 33 +/- 5 (min-1) and 7 +/- 2 for the nitrogen mustard and 29 +/- 5 and 6 +/- 1 for the saline group, respectively. These variables were ninefold higher than their corresponding values in animals breathing air. We concluded that neutrophils do not play a significant role during the early stages of sublethal hyperoxic injury to rabbit alveolar epithelium.     

Effect of naloxone on the secretion of LH in infantile and prepubertal Holstein bull calves

Administration of naloxone (100 mg i.v.; approximately 1.21 mg/kg body weight0.75) to 10 intact calves (24 weeks of age) caused an acute release of LH that was similar in amplitude and duration to spontaneous discharges of LH that occur at the same age. The naloxone-induced release of LH was abolished in 9/10 calves (intact and castrated) treated with oestradiol-17 beta. To determine the ontogeny of opioid control of secretion of LH, 12 calves were randomly assigned to receive saline or naloxone (1.21 mg/kg body weight0.75, i.v.) at 3, 5, 7, 9, 11, 13, 17 and 21 weeks of age. At each age, blood was collected at 10-min intervals for 4 h and saline or naloxone was administered (i.v.) after collection of the 120-min sample. Before administration of naloxone, plasma LH values increased with age (P less than 0.01) but did not differ between the control and naloxone groups (age x treatment, P greater than 0.05). Administration of naloxone caused concentrations of plasma LH to increase at 3, 11, 13, 17 and 21 weeks of age (treatment x time, P less than 0.001). Concentrations of LH (saline vs naloxone, ng/ml) reached a maximum within 20 min after treatment at Weeks 3 (0.3 vs 1.2), 11 (0.6 vs 2.6), 13 (0.6 vs 3.7), 17 (1.1 vs 2.6), and within 40 min after treatment at Week 21 (1.0 vs 3.5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma thromboxane and prostacyclin: comparison during normal pregnancy and pregnancy complicated by hypertension

Plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of two prostanoids with opposing biological effects, TXA2 and prostacyclin, were measured by radioimmunoassay in normal pregnancy (controls) and pregnancy complicated by hypertension (PIH) from 32 to 36 (Period 1; P1) and from 36 to 40 (Period 2; P2) weeks of gestation. The plasma concentration of each compound in the control subjects was 265.6 +/- 58.4 (TXB2), 132.4 +/- 16.5 (6-keto-PGF1 alpha) for P1 (n = 10) and 142.6 +/- 11.8 (TXB2), 68.5 +/- 5.2 (6-keto-PGF1 alpha) for P2 (n = 10) respectively (pg/ml, mean +/- s.e). In the patients with PIH, TXB2 concentrations increased moderately for P1 (419.2 +/- 21.2; n = 7) and significantly (p less than 0.005) for P2 (452.8 +/- 31.0; n = 7) respectively (pg/ml, mean +/- s.e), while the plasma levels of 6-keto-PGF1 alpha revealed a slight to moderate decrease both for P1 (84.5 +/- 4.0; n = 7) and P2 (59.7 +/- 8.1; n = 7) respectively (pg/ml, mean +/- s.e). The physiological balance of TXB2 to 6-keto-PGF1 alpha was significantly greater (p less than 0.005) in the patients with PIH, where the TXB2/6-keto-PGF1 alpha ratio was 5.2 +/- 0.7 for P1 and 9.4 +/- 2.3 for P2 respectively (mean +/- s.e) compared with that of the controls, where it was 2.4 +/- 0.4 for P1 and 2.0 +/- 0.2 for P2 respectively (mean +/- s.e).(ABSTRACT TRUNCATED AT 250 WORDS)     

A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit.

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (-9.0 to -5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (-6.0 log mol/L) was significantly (p less than 0.05) impaired in the experimental group (34.3 +/- 3.8%) compared with that in the control group (79.8 +/- 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 +/- 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 +/- 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.