Pithing

Abstract: The pressor and tachycardic effects of diphenyleneiodonium (DPI), a novel inhibitor of endothelial nitric oxide synthase with chemical structure different from those of NG-substituted Arg analogs, were studied in pentobarbital-anesthetized rats. Bolus injections of DPI (0.05-1.6 mg/kg i.v.) caused transient (1-2 min in duration) and dose-dependent increases in mean arterial pressure (MAP) with ED50 of 0.22 +/- 0.02 mg/kg and maximum effect (Emax) of 58 +/- 3 mm Hg, and heart rate (HR) with ED50 of 0.26 +/- 0.03 mg/kg and Emax of 60 +/- 5 beats/min. Pretreatments with tetrodotoxin, reserpine, guanethidine, mecamylamine, but not atropine, rauwolscine, captopril nor L-Arg, attenuated the MAP and HR responses to DPI. Phentolamine and prazosin attenuated the MAP but not HR response whereas propranolol attenuated the HR but not MAP response of DPI. Pithing abolished, whereas spinal cord transection reduced, the MAP and HR responses to DPI. Pithing did not alter the pressor response but blocked the reflex bradycardic response to NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Bolus injection of a single dose of DPI (1.6 mg/kg i.v.) or NG-nitro-L-arginine increased MAP, but only DPI caused immediate and large increases (> 1 ng/ml) in plasma norepinephrine, epinephrine and moderate increase in dopamine; pretreatment with reserpine attenuated, whereas pithing abolished these increases. The increases in plasma norepinephrine and epinephrine by DPI were positively correlated to increases in MAP and HR. The results demonstrate that DPI, unlike NG-substituted Arg analogs, produces pressor and tachycardic effects via indirect activation of the sympathetic nervous system.

Abstract: In segments of the rat inferior vena cava preincubated with 3H-noradrenaline, it was examined whether presynaptic serotonin (5-HT) receptors exist on the postganglionic sympathetic nerves of the circulatory system; for this purpose the effects of 5-HT receptor agonists and antagonists on the electrically evoked 3H overflow were studied. Furthermore, vagotomized pithed rats (treated with atropine and captopril) were used to investigate the effects of these drugs on heart rate and on the tachycardia induced by electrical stimulation of the preganglionic sympathetic nerves (C7−T1) via the pithing rod; these experiments were carried out to provide evidence that the presynaptic 5-HT receptors are operative in vivo. 1. 5-HT and 5-methoxytryptamine (5-OCH3-T) concentration-dependently inhibited the electrically evoked 3H overflow from the vena cava. The inhibitory effect was more pronounced at 0.66 Hz than at 2 Hz. 8-Hydroxy-2-(di-n-propylamino)tetralin did not alter the evoked overflow. The inhibitory effect of 5-HT or 5-OCH3-T was antagonized by metitepin but not affected by ketanserin or rauwolscine. 2. In pithed rats 5-HT and 5-OCH3-T by themselves dose-dependently increased heart rate. The positive chronotropic effect of 5-HT 10 μmol/kg, which was not affected by ketanserin, was considerably decreased by desipramine, indicating that 5-HT at least at this high dose acts predominantly by a tyramine-like indirect sympathomimetic effect. The tachycardic response to 5-OCH3-T was reversed to a very slight negative chronotropic effect by ketanserin or methysergide, but was not affected by desipramine or propranolol indicating that the increase in heart rate induced by 5-OCH3-T is mediated via 5-HT2-receptors on the pacemaker cells. 3. Ketanserin-treated pithed rats were used to study the effect of 5-OCH3-T on the tachycardia induced by stimulation of the preganglionic sympathetic nerves via the pithing rod. The nerve stimulation-induced tachycardia was inhibited by 5-OCH3-T to a significantly higher extent than the tachycadia induced by infusion of noradrenaline. The inhibitory effect of 5-OCH3-T on nerve stimulation-induced tachycardia could not be antagonized by metitepin or rauwolscine; it decreased with increasing frequency of stimulation.

Abstract: Sprague-Dawley rats, normal and chemically sympathectomized with 6-hydroxy-dopamine, were trained by treadmill running. The normal rats, unlike the sympathectomized animals, showed reduction of the exercise heart rate after the training period. Compared to a sedentary control group the sympathectomized rats showed no difference in intrinsic heart rate after pithing and denervation and no increase in heart weight. The increase of the heart weight/body weight ratio after training was smaller in the sympathectomized group than in the normal one. The results show that a functioning adrenergic nervous system is necessary for an efficient adaptation to physical training. Administration of noradrenaline to pithed trained and untrained rats showed that betaadrenergic receptor sensitivity was not altered by physical training. The intrinsic heart rate of normal trained rats was lower than that of normal control rats.