Presynaptic inhibition of canine renal adrenergic nerves by acetylcholine in vivo.

Experiments were performed in anesthetized dogs to determine whether previously reported in vitro inhibition of sympathetic neurotransmitter release by acetylcholine could be demonstrated in the renal vasculature of the intact animal. Vasoconstrictor responses to renal sympathetic nerve stimulation at varying frequencies were compared to intra-arterial injections of norepinephrine before and during intra-arterial infusions of acetylcholine, 2.5--80 micrograms/min. The vasoconstrictor responses to nerve stimulation were inhibited to a greater extent than were responses to norepinephrine during infusions of acetylcholine. The inhibitory effects of acetylcholine on nerve stimulation were dose and frequency dependent. The inhibition was blocked by atropine but not altered by physostigmine. Changes in renal blood flow per se did not contribute to the inhibitory effect of acetylcholine, since another vasodilator agent, sodium acetate, did not affect the nerve stimulation-norepinephrine vasocontriction relationship. Thus, acetylcholine produced inhibition of in vivo renal sympathetic vasoconstrictor responses, and the receptor involved appears to be muscarinic.     

Prenatal cocaine exposure reduces glial cell line-derived neurotrophic factor (GDNF) in the striatum and the carotid body of the rat: implications for DA neurodevelopment

Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer, and a member of the transforming growth factor-beta superfamily. GDNF has been shown to promote the survival and morphological differentiation of dopamine (DA) neurons and increase their high-affinity dopamine uptake. In order to determine whether the mechanism for our previously observed cocaine-induced DA reductions in brain and carotid body were GDNF-mediated, we exposed Sprague-Dawley rat fetuses to cocaine via maternal subcutaneous injections (30 mg/kg b.i.d., E7-E19). Brains and carotid bodies of fetuses were excised and processed for assessment of GDNF levels using an Enzyme-Linked ImmunoadSorbent Assay (ELISA). ANOVA indicated that cocaine reduced carotid body GDNF by 36% (F((1,5))=28. 11, p<0.05) and striatal GDNF by 41% (F((1,5))=41.77, p<0.01). Although there was no interaction between drug exposure and fetal uterine position, post-hoc pairwise comparisons indicated that reductions in GDNF in the cocaine groups were due to differences at more distal positions (positions 4-8). The magnitude of the reductions in striatal GDNF (but not carotid body GDNF) in both cocaine-exposed and control fetuses followed a cervical (smallest GDNF reductions) to ovarian (greatest GDNF reductions) uterine position gradient. This pattern was similar to that which we observed in prior studies examining DA reductions in brain following prenatal cocaine exposure. The finding that cocaine reduces GDNF levels in striatum and carotid body support the hypothesis that cocaine's ability to reduce striatal and carotid body DA may be indirect through its ability to reduce GDNF. These data along with previous findings support the hypothesis that cocaine's effects on DA neurons are at least partially due to its indirect effects on trophic activity. The possible mechanisms whereby cocaine affects trophic activity are discussed.     

Evaluation of presynaptic histamine receptors in the canine renal vascular bed

Histamine has been shown to increase renal blood flow via H1- and H2-receptors. Furthermore, H2-receptors have been demonstrated to attenuate stimulation-induced release of norepinephrine. The present studies examined whether histamine has a presynaptic effect on sympathetic nerves in the canine renal vascular bed. Renal blood flow was measured in anesthetized dogs, and vasoconstrictor responses to renal nerve stimulation and i.a. injections of norepinephrine were compared before and during i.a. infusions of histamine. Histamine increased renal blood flow and decreased stimulation-induced vasoconstriction to a greater degree than norepinephrine responses. 2-(2-pyridyl)ethylamine, an H1-agonist, did not produce consistent effects. Dimaprit, an H2-agonist, produced responses similar to histamine but to a lesser extent. The H1-antagonist tripelennamine and the H2-antagonist cimetidine each minimally antagonized the effect of histamine on nerve stimulation. When both blocking agents were infused together, maximum antagonism of histamine occurred. Thus, it appears that histamine will produce a neuroinhibitory effect in the canine renal vascular bed and this effect appears to be mediated by both H1- and H2-receptors because both receptor antagonists are necessary to block this effect.     

Healing of the resected liver stump: its process and the significance of portal blood flow

In an effort to investigate the healing process of resected liver stump and the significance of portal and hepatic arterial flow. In addition to hepatectomy in the first group, an arterial and a portal branch were ligated in the second and third groups, respectively. It was demonstrated that portal branch ligation influenced a delay in healing of resected liver stump rather than hepatic arterial branch ligation. It is assumed that portal blood flow is more responsible for liver stump healing as well as hepatic regeneration than is hepatic arterial flow.