Call number: LD2668 .T4 1964 R47 / Master of Science

Call number: LD2668 .T4 1984 B37 / Master of Science

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Naloxone (NX) potentiated epinephrine (EPI) induced submaximal vasoconstriction in canine renal and skeletal muscle arterial segments, yet had no vasoconstrictor action alone. Developed tension generated in-vitro by 4 x 1mm. O.D. rings from 1st degree branches of canine femoral arteries was expressed as % of KCI induced maximum response. NX (10^-5 M) potentiated EPI induced submaximal contractions (34.2%) significantly more than contractions induced by norepinephrine, phenylephrine, lofexidine, ADH, KCI and serotonin (13.8,13.4,4.7,13.5,14.4 and 11.4% respectively). The NX response was unaffected by beta-adrenergic blockade and NX did not reverse an isoproterenol mediated vasodilation. Alphaadrenergic blockade with phentolamine completely eliminated EPI plus NX induced vasoconstriction. After washout, vessels exposed to EPI plus NX relaxed by 50% significantly faster than vessels exposed to EPI alone (18.5 and 27.9 min respectively). EPI induced vasoconstrictions were potentiated by 10^-5 M corticosterone (49.0%) which inhibits extraneuronal catecholamine uptake, but not by 10^-7 M desipramine (1.1%) which inhibits neuronal uptake. EPI induced vasoconstrictions were also potentiated by 10^-4 M pyrogallol (33.0%) which inhibits catechol-o-methyl transferase activity, but not by 10^-5 M pargyline (-1.1%) which inhibits monoamine oxidase activity. The NX effect was endothelium independent. The dose-response of various opioid receptor agonists and antagonists were compared to the NX response. A specific opioid receptor subclass could not be identified as the mediator of the NX effect. The ED_50s for NX (3.7x^-6 M) and (+)NX (8.1x^-7M) indicated a significant stereoselectivity for the (+)enantiomer. A variety of sigma receptor ligands, steroids and steroid metabolites were tested for the ability to augment EPI vasoconstrictions. Several of the opioid, sigma and steroid ligands, all with polycyclic structures, induced responses similarto those of NX. NX exerted its effect independent of traditional opiate receptors and may have influenced the cellular uptake or degradation of EPI. Endogenous compounds with sigma or steroid activity may modulate these processes in-vivo.

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Call number: LD2668 .T4 1985 D42 / Master of Science

Eighteen healthy dogs were divided into three equal groups. All dogs were evaluated at the beginning of the experiment with complete physical examination, complete blood count, serum alanine aminotransferase, serum alkaline phosphatase, serum bilirubin, serum albumin, sulfobromophthalein. excretion test, ammonia tolerance test, glucagon response test, portal and intraparenchymal pressures, operative mesenteric portography, and histologic assessment of hepatic tissue. The left hepatic vein was ligated in the chronic and acute dogs. The dogs had a ligature placed loosely around the left hepatic vein. Acute and control dogs were evaluated 24 hours postoperatively with the hematologic and biochemical tests listed above. Acute dogs were evaluated with portal and intraparenchymal pressure, operative mesenteric portography and histologic evaluation of hepatic tissue at 48 hours postoperatively. Chronic and control dogs were evaluated at 4 weeks postoperatively with all of the tests listed above. The results of all tests performed supported a transient hepatic congestion which resolved bv the fourth postoperative week. No longstanding effect on hepatic function was found. The conclusion of this experiment was that, in normal dogs, left hepatic vein ligation does not cause severe or permanent liver damage. These findings support a clinical trial of this procedure in patients with patent ductus venosus. / Master of Science