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R E Stitzel

Publications and source records attributed to R E Stitzel.

At least 37 records · Page 2Linked to original sources
PubMed1985

Hypernoradrenergic innervation of the caudal artery of the spontaneously hypertensive rat: an influence upon neuroeffector mechanisms.

In the present studies we have established that the perfused caudal artery from spontaneously hypertensive (SH) rats responds to pharmacological and physiological stimuli in a manner similar to that described for other blood vessels from the SH rat. In addition, the responses of caudal arteries from SH rats to exogenous norepinephrine were similar to those of arteries removed from normotensive Kyoto Wistar rats. However, responses to sympathetic nerve stimulation at high, but not low, frequencies of stimulation were increased in arteries from the SH rat. In addition, impairment of neuronal uptake with cocaine unmasked a greater responsiveness of arteries from SH rats to sympathetic nerve stimulation. Consistent with the latter finding the neuronal uptake and neuronal deamination of norepinephrine was larger in caudal arteries from SH rats. A histofluorescent and electron microscopic analysis of the sympathetic innervation of caudal arteries from SH and Kyoto Wistar rats demonstrated that the vessels from SH animals had a greater number of nerve axon bundles and a greater area of adventitia occupied by nerve bundles. It is concluded that the ability of high rates of nerve stimulation and cocaine to unmask an enhanced responsiveness of caudal arteries from SH rats is related to an enhanced innervation of the artery. It is suggested that in the SH rat model of hypertension future research into the causes of the augmented blood pressure should be directed toward factors regulating the density of the sympathetic innervation of the vasculature.

Animals↗
PubMed1984

Non-radiochemical procedure for the measurement of O-methylation of the stereoisomers of isoprenaline.

A non-radiochemical procedure has been developed which permits the separation and measurement of isoprenaline (ISO) and the O-methylated metabolite, 3-methoxyisoprenaline (MeOISO). This methodology employs alumina chromatography and toluene solvent extraction to separate the catecholamine, ISO, from the O-methylated derivative, MeOISO. High-performance liquid chromatography with electrochemical detection has been used to quantify these compounds. The biological application of this procedure includes the evaluation of O-methylation of the stereoisomers of ISO by intact tissues.

Animals↗
PubMed1984

Neuronal deamination of endogenous and exogenous noradrenaline in the mesenteric artery of the spontaneously hypertensive rat.

The noradrenaline (NA) content of the mesenteric arteries from spontaneously-hypertensive rats (SHR) are greater than those in arteries from normotensive Kyoto Wistar rats (WKY). The possibility that impaired neuronal monoamine oxidase (MAO) activity in mesenteric arteries from SHR rats was responsible for the differences in NA content was explored. The in-vitro formation of dihydroxyphenylethylene glycol (DOPEG) by intact segments of mesenteric arteries was used as an index of neuronal MAO activity. There were no differences in the production of DOPEG from endogenous NA by arteries from normotensive and hypertensive rats. Moreover, the formation of DOPEG from exogenous NA was similar in arteries from SHR and WKY rats. The neuronal uptake of NA was indistinguishable between mesenteric arteries from SHR and WKY rats. The results argue against an impairment of neuronal MAO in contributing to the enhanced content of NA in the mesenteric artery of the SHR rat.

Animals↗
PubMed1980

Changes in adrenal microsomal cytochrome(s) P-450 with aging in the guinea pig.

Studies were carried out to investigate the mechanism(s) responsible for the changes in adrenal microsomal mixed function oxidase activity which occur with aging (30-200 days) in guinea pigs. With aging, the rate os metabolism of xenobiotics [ethylmorphine and benzo(a)pyrene] by adrenal microsomes increased 3- to 5-fold. Steroid 17 alpha- and 21-hydroxylations, when expressed per mg protein, were similar in immature (30 days old) and mature (200 days old) animals. Adrenal microsomal NADPH- and NADH-cytochrome c reductase activities and cytochrome b5 concentrations increased wih aging, but cytochrome P-450 concentrations were not significantly different in young and old guinea pigs. Maximal type I difference spectra produced by steroids were the same in adrenal microsomes from 30- and 200-day-old guinea pigs, but the ethylmorphine-induced spectrum was far greater in the older animals. Progesterone enhanced NADPH-cytochrome P-450 reductase activity to about the same extent in adrenal microsomes from 30- and 200-day-old guinea pigs. Ethylmorphine had no effect on the rate of reduction of cytochrome P-450 in adrenals from young animals but produced a 4-fold increase in activity in adrenals from older animals. The results demonstrate selective changes in adrenal xenobiotic metabolism with aging and suggest that changes in the composition and/or reactivity of adrenal cytochromes P-450 are responsible for the effects of aging.

Adrenal Glands↗
PubMed1978

The postjunctional effects and neural release of purine compounds in the guinea-pig vas deferens.

The smooth muscle of the in vitro guinea-pig vas deferens was shown to contract upon addition of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP), the order of potency being ATP greater than ADP greater than AMP. Adenosine did not produce contraction. Pretreatment of animals with reserpine or treatment of tissues with an alpha-adrenoceptor blocking agent failed to alter the dose-response relationship for ATP. Because ATP is both a potent contractile agent and is present in the adrenergic storage complex, evidence was sought for the role of ATP as a possible co-transmitter following neural stimulation. Tissues preincubated in 3H-adenosine, a procedure which results in the incorporation of label into 3H-adenine nucleotides in the vas deferens, released significant amounts of tritium upon transmural stimulation. Because contraction per se can contribute to the tritium overflow, experiments were conducted with bathing solution made hypertonic with sucrose (12.5%). Hypertonic solution prevented the electrically induced tissue contraction, but failed to prevent a tetrodotoxin-sensitive release of tritium from tissue preincubated with either 3H-norepinephrine or 3H-adenosine. Because of the known association of ATP with norepinephrine in synaptic vesicles of adrenergic nerves and in view of the present evidence of a postjunctional action of ATP as well as the release of tritium from 3H-adenosine-treated vasa deferentia, it seems possible that in this tissue ATP, in addition to its other functions, may serve as a co-transmitter with norepinephrine.

Adenine Nucleotides↗
PubMed1977

Effect of chronic denervation on the activities of monoamine oxidase and catechol-O-methyl transferase and on the contents of noradrenaline and adenosine triphosphate in the rabbit ear artery.

When assayed on homogenates of the rabbit ear artery up to 192 h after sympathetic denervation, the activity of monoamine oxidase (MAO) showed a small but significant decrease (maximum 9%). The activity of catechol-O-methyl transferase (COMT) appeared unchanged, although it is possible that the small and variable nature of this enzyme activity compared with that of MAO may have masked a comparable effect of denervation. The maximum decreases in noradrenaline (NA) and adenosine triphosphate (ATP) contents were greater than 90% at 48 h, and 32% at 96 h after denervation. These results confirm the presence of neuronal as well as extra-neuronal MAO, and also the presence of extraneuronal comt in this artery. The decline in ATP contents after denervation suggest that part of the ATP is neuronal. However, the estimated ratio of NA to neuronal ATP is far in excess of that reported for isolated noradrenaline storage vesicles, suggesting that the major portion of the neuronal ATP was not present in these vesicles.

Adenosine Triphosphate↗
PubMed1976

The biological fate of reserpine.

Orally administered reserpine is readily absorbed from the GI tract. During this process at least a portion of the drug is metabolized by the intestinal mucosa and then presumably is acted upon by serum esterases. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from the hydrolytic cleavage of reserpine. Since most of the blood leaving the GI tract passes through the liver via the portal vein, hepatic metabolism would also be expected to reduce reserpine levels in the blood. The relative contributions of serum esterases versus hepatic metabolism in the biotransformation of reserpine in vivo are not known. However, very little unmetabolized reserpine is eventually eliminated in the urine. In the liver, it is quite likely that both microsomal oxidative and hydrolytic enzymes contribute to the metabolism of reserpine. It seems that microsomal oxidation (such as the demethylation of the 4-methoxy group on the TMBA moiety) must precede hydrolysis since inhibition of demethylation markedly reduces the rate of hydrolysis. In addition to oxidation and hydrolysis, conjugative reactions also must occur in liver or extrahepatic tissues since both glucuronide and sulfate conjugates of TMBA have been identified. Some reserpine molecules do seem to escape metabolism, however, since significant amounts of intact reserpine have been found in fecal samples taken from both experimental animals and human beings after either oral or parenteral drug administration. Presumably reserpine is transported from the blood via the biliary tree into the small intestine where it is either reabsorbed or eliminated in the feces. Pulmonary elimination of CO2 produced after complete oxidation of the 4-methoxy group of TMBA has also been shown to occur both in vivo and in vitro. The following may serve as a model for the relationship between the subcellular distribution of reserpine and its site of action. After a single intravenous injection most of the reserpine, probably loosely bound to plasma albumin, is distributed to tissues on the basis of their blood flow. Because of its lipophilic properties, reserpine would easily penetrate cell membranes and then bind possibly electrostatically to intracellular membrane components, particularly those rich in phospholipids. Much of the circulating reserpine would then either be metabolized or be taken up by the lipid depots of the body, leading to a rapid redistribution of the reversibly bound reserpine from the tissues. During this time a relatively small fraction of the total reserpine administered by injection would become associated with monoaminergic granular membranes in a more specific and irreversible manner. This would result in a persistent, nonstoichiometric inhibition of monoamine uptake. Such a small specific binding would not be detectable for at least 18 hr after reserpine administration, i.e., until most of the reversibly bound alkaloid had been metabolized and/or excreted...

Animals↗
PubMed1975

Effects of various denervation techniques on the ATP of the rat vas deferens.

Postganglionic denervation of the vas deferens of the rat by surgical means or pretreatment with 6-hydroxy-dopamine results in a substantial decrease in the concentration of ATP in the tissue. The loss of ATP cannot entirely be accounted for by the loss of neuronal ATP nor by a compromised blood supply. The results suggest that the postganglionic nerve plays an important role in the regulation of the ATP of the effector cells.

Adenosine Triphosphate↗
PubMed1975

Morphological and biochemical changes in supersensitive smooth muscle.

The effect of postganglionic denervation on the incidence of nexal contacts in the smooth muscle of the rat vas deferens was investigated. The chronically denervated tissue exhibited twice as many nexuses as control. This increase in the incidence of cell contacts may contribute to the supersensitivity and/or the increase in maximum response of the denervated vas deferens. The effects of denervation, decentralization, and pretreatment with reserpine on the concentration of adenosine triphosphate (ATP) in vasa deferentia of rats and guinea pigs were also investigated. One day after denervation there was a substantial decrease in the endogenous norepinephrine and ATP concentrations. The norepinephrine concentration remained low (less than 10% of control) throughout subsequent days (up to 14 days) whereas the ATP concentration, after the first postoperative day, rose significantly. The rise in ATP concentration was temporally correlated with the development of postjunctional supersensitivity. Decentralization and pretreatment with reserpine both resulted in a significant increase in ATP concentration which preceded by 2 to 3 days a significant increase in sensitivity of the vas deferens. It appears that a change in the tissue concentration of ATP may be one of the initial events that occurs following interruption of the neural contact to the smooth muscle of the vas deferens.

Adenosine Triphosphate↗