Lanthanum inhibits 45 Ca efflux from internally injected squid axons. • Peripheral resistance is a function of the contractile state of arterial smooth muscle cells. Since motor innervation to arterial muscle is mainly by norepinephrine-secreting sympathetic neurons, antihypertensive therapy and research have focused on inhibition of the sympathetic nervous system. However, it has thus far been impossible to establish a cause and effect relationship between malfunction of the autonomic nervous system and

The study of cellular Ca 2+ exchange in smooth muscle has been severely limited by extensive extracellular Ga 2+ binding. This problem was solved by using La 3+ to trap Ca 2+ inside the cells while displacing extracellular bound Ca 2+ . It was then shown that cytoplasmic Ca 2+ could be raised by Ca 2+ influx during high K+ depolarization, Na+ elimination and high pH. Ca 2+ influx was inhibited by other multivalent cations, local anaesthetics and low pH. In the rabbit aortae norepinephrine and angiotensin increase cytoplasmic Ca 2+ by release from intracellular membrane surfaces. In this same smooth muscle relaxation is brought about by intracellular Ca 2+ binding. Evidence from vascular, uterine and intestinal smooth muscle demonstrates that the large transmembrane Ca 2+ gradient depends on cellular [ATP] but not on the Na+ gradient. ATP depletion abolishes the Ca 2+ gradient by increasing Ca 2+ influx.

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Nicotinate is readily converted to NAD in animal tissues. The pathway involves nicotinate mononucleotide and nicotinate adenine dinucleotide as intermediates ( 1, 2 ) . Animal tissue also contains enzyme (s) having NAD glycohydrolase activity that breaks N&AD down to nicotinamide and adenosine diphosphoribose (3). The administration of low levels of nicotinate to mice results in a marked increase in hepatic nicotinamide levels (4) presumably from NAD via NAD glycohydrolase. This observation that nicotinate appears to be a more efficient precursor of hepatic nicotinamide than nicotinamide itself motivated us to explore the matter further. The results presented here indicate that hyperphysiological levels of hexestrol cause a marked alteration in the means whereby nicotinate is converted to nicotinamide in mice.Materials and Methods. The C57 black male mice (25-35 g) received hexestrol or sesame oil intramuscularly as described in the tables. The 14C-nicotinate was administered by intravenous injection at the level indicakd. The animals were sacrificed by cervical rupture a t the time indicated, the livers immediately removed and dropped into a dry ice-acetone freezing mixture. Individual frozen livers were dropped into 3 ml of boiling 0.04 M potassium phosphate buffer, p H 5.4.After 1 min in a boiling water bath the samples were homogenized for 30 sec, cooled in an ice bath and centrifuged a t 21,OOOg for 15 min. Carrier NAD, nicotinamide, and nicotinate where then added to the supernatant fluid and aliquots were applied to sh,eets of 1This study was supported by Grants CA 04868 and AM 03049 and a Career Development Award Health Service 6) from the United States Public Whatman 3MM paper. The sheets were developed in either the isobutyrate-NHS solvent of Magasanik et al. (4), or in butanol saturated with water containing solid NH4HC03 ( 5 ) . The spots corresponding to NAD, nicotinamide, and nicotinate were cut out and quantitated for radioactivity (6).Results and Discussion. The intravenous administration of tracer amounts of I Tnicotinate (1.5-7.5 pg) (Table I, Fig. 1) results in the following events: (i) The intrahepatic levels of labeled nicotinate decreases rapidly during the first few minutes after intravenous injection. This is evident in the case of intraportal injection. The level of nicotinate then gradually increases at a linear rate during the experimental period (60 min). The rapid disappearance of labeled nicotinate from the liver under these conditions is in keeping with the findings of Ijichi ct al. (7).(ii) Hepatic NAD and nicotinamide are rapidly labeled, significant amounts of these labeled compounds appearing in less than 0.2 or 1 min in the cases of intraportal or tail vein administration, respectively. These latter data are illustrated in Fig. 1 where the percentage change in specific activity is plotted against time, employing the values obtained a t 1 min as 100%. One-min values of 4497 cpm/pmole of NAD and 575 cpm/pmole of nicotinamide were obtained upon administration of nicotinate-l*C via...