The kinetic features of the interaction of dihydropyridines with rat aortic smooth muscle were investigated in parallel mechanical and binding studies. The inhibitory action of (+ )-PN200-110 and nisoldipine on contractions evoked by potassium chloride depolarization was characterized by a pronounced time dependency, in which the inhibition increased slowly after depolarization to attain a steady-state value, while with (-)-PN200-110 and ( + )-Bay K8644 the inhibition was almost instantaneous. To explain these observations, specific binding sites for dihydropyridines were studied in membranes isolated from rat aorta, using [ 3 H]( + )-PN200-l 10 as a radioligand. We found that the time course of the development of inhibition of potassium chloride-evoked contractions by various concentrations of (+ )-PN200-110 paralleled the time course of [3H]( + )-PN200-l10 binding to isolated membranes and that the level of inhibition was predictable from the level of occupation of these binding sites. These results indicate that depolarization increases the affinity of calcium channels for dihydropyridines in vascular smooth muscle and that the time course of the inhibitory effect on contraction is determined by the time course of association with the high-affinity state of the channel.

Some hematological and cardiovascular parameters of the underweight neonatal piglets have been compared with normal-weight 1 and 7-day-old swine (Sus scrofa domestica). The underweight swine had a significantly lower leukocyte count, plasma protein level and blood glucose level, but a significantly higher plasma LDH level. Heart rate and arterial blood pressure were significantly lower in the underweight group. Based on the observed results it was postulated that the piglets born with a low body weight could also be physiologically immature since the cardiovascular parameters measured approximated those reported for normal fetuses of the same weight. Further studies are required to ascertain if a functional immaturity persists in the neonatal animals.

In order to determine skeletal muscle and serum enzyme activities following exercise, six adult Landrace pigs were submitted to 10 min running on a treadmill (0.5 m/s, on a 12% gradient) and compared to six controls. Blood samples were obtained just before the exercise, immediately after, and 24 h, 48 h and 144 h after exercise. Muscle biopsies were taken from the longissimus dorsi and biceps femoris 24 h after exercise. Total lactic dehydrogenase (LDH) and LDH isoenzymes in muscle and serum were unchanged. In muscle homogenates, there was no difference in total creatine phosphokinase (CK) activity between the two groups. Total CK activity in the biceps femoris muscle represented only 59% of that observed in the longissimus dorsi muscle. A mean CK-MB value of 2.5% was found in the control group for both muscles but after exercise it was 9.5% (p less than 0.05) for the biceps femoris and 12.2% (p less than 0.01) for the longissimus dorsi muscle. In serum, the total CK (p less than 0.05), CK-MM (p less than 0.05) and CK-BB (p less than 0.05) increased immediately after the exercise, followed by a progressive decrease.

1 Isolated lung parenchymal strips of the dog contracted in response to histamine > carbachol > prostaglandin F2 , (PGF2#J> bradykinin (Bk) > 5-hydroxytryptamine (5-HT). The order of the relative activity of these agents on the tracheobronchial smooth muscles (TBSM) was carbachol'> 5-HT > histamine; PGF2. and Bk were inactive. Thus there are marked differences in the responsiveness of the smooth muscle of central (trachea and bronchus) and peripheral (lung strip) airways to autonomic and autacoid agents. 2 Lung strips and TBSM partially contracted by carbachol, histamine or horse plasma, were relaxed by isoprenaline, PGE1 and PGE2. 3 Lung strips from dogs sensitized to horse-plasma contracted in response to antigen (Schultz-Dale anaphylactic reaction). Tachyphylaxis or desensitization to subsequent antigen challenge was invariably observed; it was followed after 1 to 2 h of rest by partial recovery of the anaphylactic response.

Isolated guinea-pig lung parenchymal strips (GPLS) relaxed in response to the selective histamine H₂-receptor agonists, dimaprit and 4-methylhistamine (4-MeH), and to low doses of histamine (10^–9 to 10^–7 mol/l) and contracted in response to several spasmogens. The order of the relative activity of the spasmogens was 2-methylhistamine (2-MeH) > histamine > carbachol > 2-pyridylethylamine (2-PE). Dimaprit and 4-MeH also relaxed GPLS which were contracted by 2-MeH, 2-PE or carbachol. Metiamide (a selective H₂-antagonist: 5 x 10^–5 mol/l inhibited or reversed relaxations to histamine, dimaprit and 4-MeH, and significantly enhanced contractile responses to histamine without altering responses to carbachol. Mepyramine (a selective Hi-receptor antagonist: 10^–8 to 10^–6 mol/l antagonized histamine-induced contractions. This investigation shows: (1) histamine is more active than carbachol in GPLS and (2) the occurrence of histamine Hi-receptors mediating contraction and H₂-receptors mediating relaxation in guinea-pig lung.