Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of K(Ca) channels.

O(2) sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O(2) tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 +/- 1.7% decrease in intracellular calcium in response to an acute increase in O(2) tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O(2) was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited "spontaneous transient outward currents," indicative of intracellular calcium spark activation of calcium-sensitive potassium channels. The frequency of spontaneous transient outward currents increased when O(2) tension was increased to normoxic levels. Increasing fetal pulmonary O(2) tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O(2)-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O(2) tension and that this O(2) response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.

Pulmonary vascular response to normoxia and K(Ca) channel activity is developmentally regulated.

To address developmental regulation of pulmonary vascular O(2) sensing, we tested the hypotheses that 1) fetal but not adult pulmonary artery smooth muscle cells (PASMCs) can directly sense an acute increase in O(2), 2) Ca2+-sensitive K(+) (K(Ca)) channel activity decreases with maturation, and 3) PASMC K(Ca) channel expression decreases with maturation. We used fluorescence microscopy to confirm that fetal but not adult PASMCs are able to sense an acute increase in O(2) tension. Acute normoxia induced a 22 +/- 2% decrease in cytosolic Ca2+ concentration ([Ca2+](i)) in fetal PASMCs and no change in ([Ca2+](i)) in adult PASMCs (P < 0.01). The effects of K(+) channel antagonists were studied on fetal and adult PASMC ([Ca2+](i)). Iberiotoxin (10(-9) M) caused PASMC ([Ca2+](i)) to increase by 694 +/- 22% in the fetus and caused no change in adult PASMCs. K(Ca) channel expression and mRNA levels in distal pulmonary arteries from fetal and adult sheep were examined. Both K(Ca) channel protein and mRNA expression in the distal pulmonary vasculature decreased with maturation. We conclude that maturation-dependent changes in PASMC O(2) sensing render the fetal PASMCs uniquely sensitive to an acute increase in O(2) tension at a biologically critical time point.

The effects of endophyte-infected tall fescue consumption and use of a dopamine antagonist on intake, digestibility, body temperature, and blood constituents in sheep.

Two experiments were conducted with lambs that consumed endophyte-infected (Acremonium coenophialum) tall fescue diets under elevated temperature and humidity and supplemented with the dopamine antagonist metoclopramide (M). In Exp. 1, 12 ruminally cannulated wethers (average weight 49 kg) were allotted by weight to either an endophyte-free diet (E-) or endophyte-infected diet (E+; 1,170 ppb of ergovaline), or E+ supplemented with M (15 mg/kg of lamb BW; E+M). Ad libitum DM intake and digestibility were lower (P < .05) for E+ than for E- diet. Supplementation of E+ with M increased (P < .05) DM intake by 27.6% but did not change DM digestibility. Body temperature increased (P < .05) when lambs consumed E+ and was further increased when M was supplemented. For Exp. 2, 19 wether lambs (average weight 24 kg) were allotted to treatments to evaluate the effects of endophyte consumption (0 vs 2,430 ppb of ergovaline) and supplementation with M (0 vs 20 mg/kg BW). An interaction (P < .05) of main effects was measured for DM intake. Lambs that consumed E+M consumed more DM than did lambs fed only E+, but lambs offered the E- diet and supplemented with M did not increase DM consumption. Diet DM digestibility was not different among treatments. Skin vaporization decreased (P < .05) due to E+ consumption and M supplementation. The concentration of prolactin in plasma was decreased (P < .05) by consumption of E+ (8 vs 136 ng/mL) and did not increase due to M supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced blood flow to peripheral and core body tissues in sheep and cattle induced by endophyte-infected tall fescue.

Four wethers and 14 steers (environmentally heat stressed, 32 degrees C, 60% relative humidity) were evaluated for changes in blood flow induced by endophyte-infected tall fescue. Concentration of the ergopeptide ergovaline was used as an indicator of diet toxicity due to the endophytic fungus Acremonium coenophialum. Blood flow to specific tissues was measured using radiolabeled microspheres. Wethers received one of two dietary treatments for 30 d before determination of tissue blood flow: 1) a low-endophyte diet (less than .05 ppm ergovaline) or 2) a high-endophyte (1.18 ppm ergovaline) diet. Blood flows to the adrenal glands and skin covering the inner hind leg were less (P less than .10) in wethers consuming the high-endophyte diet than in those consuming the low-endophyte diet. Tissue blood flows in steers were determined on two occasions: 1) after steers had received a low- (less than .01 ppm ergovaline) or high-endophyte (.52 ppm ergovaline) fescue diet for 14 d and 2) 8 d after steers had been switched to a common, fescue-free diet. Blood flows to skin covering the ribs, cerebellum of the brain, duodenum, and colon were less (P less than .10) in steers consuming the high-endophyte diet. However, 8 d after consuming fescue-free diets, steers that had previously consumed the high-endophyte diet had greater (P = .08) blood flow to the coronary bands of the front hooves than steers that had consumed the low-endophyte diet. Blood flows to all other tissues were similar between treatments. We inferred from these experiments that the toxin(s) associated with endophyte-infected tall fescue caused decreased blood flow to peripheral and core body tissues and that this effect was abated within 8 d of removing the toxin(s).

Flushing and altrenogest affect litter traits in gilts.

Gilts (n = 267) were allotted to flushing (1.55 kg/d additional grain sorghum), altrenogest (15 mg.gilt-1.d-1) and control treatments in a 2 x 2 factorial arrangement. Altrenogest was fed for 14 d. Flushing began on d 9 of the altrenogest treatment and continued until first observed estrus; 209 gilts (78%) were detected in estrus. The interval from the last day of altrenogest feeding to estrus was shorter (P less than .05) with the altrenogest + flushing treatment (6.6 +/- .2 d) than with flushing alone (7.6 + .3 d). Ovulation rates (no. of corpora lutea) were higher (P less than .05) in all flushed gilts (14.5 +/- .4 vs 13.4 +/- .4), whether or not they received altrenogest. Flushing also increased the total number of pigs farrowed (.9 pigs/litter; P = .06) and total litter weight (1.43 kg/litter; P = .01), independent of altrenogest treatment. Number of pigs born alive and weight of live pigs were higher for gilts treated with altrenogest + flushing and inseminated at their pubertal estrus than for gilts in all other treatment combinations. In contrast, gilts receiving only altrenogest had greater live litter weight and more live pigs born when inseminated at a postpubertal estrus than when inseminated at pubertal estrus. We conclude that flushing increased litter size and litter weight, particularly for gilts that were inseminated at their pubertal estrus. Increased litter size resulted from increased ovulation rates, which, in nonflushed gilts, limited litter size at first farrowing.