Arthrogryposis, hydranencephaly and cerebellar hypoplasia syndrome in neonatal calves resulting from intrauterine infection with Aino virus

To determine the teratogenic potential of Aino virus (AINOV) in cattle, pregnant cows and fetal cattle were infected with a fresh isolate of AINOV. Five pregnant cows were inoculated intravenously with the virus at 122 to 162 days of gestation and allowed to give birth. All of the cows developed neutralizing antibodies to the virus, indicating that the cows had been infected with the virus; however, no clinical abnormalities were seen in their six newborn calves, and no specific antibodies to the virus were detected in the precolostral serum of calves. Five fetuses with fetal ages ranging from 132 to 156 days were inoculated in utero with the virus. One weak newborn and four stillborn calves were delivered at gestation days 256 to 263, i.e., less than the standard gestation term; they had congenital abnormalities including arthrogryposis, hydranencephaly and cerebellar hypoplasia. Antibodies specific to AINOV were detected in their precolostral serum. These results demonstrate that AINOV is a potential etiological agent of congenital malformation of cattle

Possible mechanisms underlying the vasodilatation induced by olprinone, a phosphodiesterase III inhibitor, in rabbit coronary artery

1. The possible mechanisms underlying the vasodilatation induced by olprinone, a phosphodiesterase type III inhibitor, were investigated in smooth muscle of the rabbit coronary artery. Isometric force and membrane potential were measured simultaneously using endothelium-denuded smooth muscle strips. 2. Acetylcholine (ACh, 3 μM) produced a contraction with a membrane depolarization (15.2±1.1 mV). In a solution containing 5.9 mM K(+), olprinone (100 μM) hyperpolarized the resting membrane and (i) caused the absolute membrane potential level reached with ACh to be more negative (but did not reduce the delta membrane potential seen with ACh, 15.2±1.8 mV) and (ii) attenuated the ACh-induced contraction. In a solution containing 30 mM K(+), these effects were not seen with olprinone. 3. Glibenclamide (10 μM) blocked the olprinone-induced membrane hyperpolarization. 4-AP (0.1 mM) significantly attenuated the olprinone-induced resting membrane hyperpolarization but TEA (1 mM) had no such effect. 4. Glibenclamide (10 μM), TEA (1 mM) and 4-AP (0.1 mM), given separately, all failed to modify the inhibitory actions of olprinone on (i) the absolute membrane potential level seen with ACh and (ii) the ACh-induced contraction. 5. It is suggested that olprinone inhibits the ACh-induced contraction through an effect on the absolute level of membrane potential achieved with ACh in smooth muscle of the rabbit coronary artery. It is also suggested that glibenclamide-sensitive, ATP-sensitive K(+) channels do not play an important role in the olprinone-induced inhibition of the ACh-induced contraction

Possible mechanisms underlying the midazolam-induced relaxation of the noradrenaline-contraction in rabbit mesenteric resistance artery

1. The mechanisms underlying the midazolam-induced relaxation of the noradrenaline (NA)-contraction were studied by measuring membrane potential, isometric force and intracellular concentration of Ca(2+)([Ca(2+)](i)) in endothelium-denuded muscle strips from the rabbit mesenteric resistance artery. The actions of midazolam were compared with those of nicardipine, an L-type Ca(2+)-channel blocker. 2. Midazolam (30 and 100 μM) did not modify either the resting membrane potential or the membrane depolarization induced by 10 μM NA. 3. NA (10 μM) produced a phasic, followed by a tonic increase in both [Ca(2+)](i) and force. Midazolam (10–100 μM) did not modify the resting [Ca(2+)](i), but attenuated the NA-induced phasic and tonic increases in [Ca(2+)](i) and force, in a concentration-dependent manner. In contrast, nicardipine (0.3 μM) attenuated the NA-induced tonic, but not phasic, increases in [Ca(2+)](i) and force. 4. In Ca(2+)-free solution containing 2 mM EGTA, NA (10 μM) transiently increased [Ca(2+)](i) and force. Midazolam (10–100 μM), but not nicardipine (0.3 μM), attenuated this NA-induced increase in [Ca(2+)](i) and force, in a concentration-dependent manner. However, midazolam (10 and 30 μM), had no effect on the increases in [Ca(2+)](i) and force induced by 10 mM caffeine. 5. In ryanodine-treated strips, which have functionally lost the NA-sensitive Ca(2+)- storage sites, NA slowly increased [Ca(2+)](i) and force. Nicardipine (0.3 μM) did not modify the resting [Ca(2+)](i) but partly attenuated the NA-induced increases in [Ca(2+)](i) and force. In the presence of nicardipine, midazolam (100 μM) lowered the resting [Ca(2+)](i) and further attenuated the remaining NA-induced increases in [Ca(2+)](i) and force. 6. The [Ca(2+)](i)-force relationship was obtained in ryanodine-treated strips by the application of ascending concentrations of Ca(2+) (0.16–2.6 mM) in Ca(2+)-free solution containing 100 mM K(+). NA (10 μM) shifted the [Ca(2+)](i)-force relationship to the left and enhanced the maximum Ca(2+)-induced force. Under these conditions, whether in the presence or absence of 10 μM NA, midazolam (10 and 30 μM) attenuated the increases in [Ca(2+)](i) and force induced by Ca(2+) without changing the [Ca(2+)](i)-force relationship. 7. It was concluded that, in smooth muscle of the rabbit mesenteric resistance artery, midazolam inhibits the NA-induced contraction through its inhibitory action on NA-induced Ca(2+) mobilization. Midazolam attenuates NA-induced Ca(2+) influx via its inhibition of both nicardipine-sensitive and -insensitive pathways. Furthermore, midazolam attenuates the NA-induced release of Ca(2+) from the storage sites. This effect contributes to the midazolam-induced inhibition of the NA-induced phasic contraction