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Biomedical subjects

R J Head

Publications and source records attributed to R J Head.

At least 73 records · Page 4Linked to original sources

Surgical sympathectomy of the heart in rodents and its effect on sensitivity to agonists.

A new procedure for sympathetic denervation of the hearts of rats and guinea pigs is described. Bilateral removal of the inferior and medial cervical ganglia results in almost complete loss of catecholamines from atria and ventricles, disappearance of catecholamine-associated histofluorescence from the region of the sinoatrial node and marked depression of the chronotropic concentration-response curve for tyramine in right atria of both species. Seven days after bilateral sympathectomy, the chronotropic concentration-response curve for isoproterenol is shifted to the left by a factor of 3.3 in the rat and 1.7 in guinea-pig right atria. The chronotropic concentration-response curve for histamine was not shifted by sympathectomy in the guinea-pig right atrium. Inasmuch as the rat atrium does not respond to histamine, similar experiments could not be done in the rat. The inotropic concentration-response curve for isoproterenol in electrically driven left atria was not affected by 7 days of sympathectomy in either species. These results indicate that chronic surgical sympathectomy of the heart can be successfully accomplished in the rat and guinea pig. Such sympathectomy induces a postjunctional supersensitivity in guinea-pig right atria which is qualitatively and quantitatively similar to that described previously for chronic treatment with reserpine. Bilateral surgical sympathectomy provides a valuable tool for future investigations of the cellular basis of supersensitivity in the myocardium.

Animals↗

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↗

Responses of the isolated perfused mesenteric vasculature from diabetic rats: the significance of appropriate control tissues.

The influence of streptozotocin-induced diabetes on the contractile responses of the rat isolated perfused mesenteric vascular bed was determined. Two control groups were used, age-matched, fed ad-libitum rats and age-matched, food-restricted rats which were weight-matched to the diabetic group. Two months after the induction of diabetes there was a nonspecific decrease in contractile responsiveness of the mesenteric vascular bed from the diabetic rats to nerve stimulation, and to intraluminal norepinephrine and KCI compared to the responses of the control groups. There was no difference in the responsiveness of the two control groups to these vasoconstrictor treatments. The diabetes-induced depression of responses could be due to changes in vascular smooth muscle function, with an additional contribution of an abnormality in sympathetic neuronal function.

Animals↗

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↗

High-pressure liquid chromatographic-fluorometric detection of adenosine and adenine nucleotides: application to endogenous content and electrically induced release of adenyl purines in guinea pig vas deferens.

To avoid some of the disadvantages associated with using radiolabeling to investigate adenyl purine content and release from excitable tissues, a reverse-phase high-pressure liquid chromatographic method utilizing fluorescence detection for the measurement of picomole amounts of endogenous ATP and its 6-amino purine analogs has been developed. This procedure has been used to determine the content of adenyl purines in the guinea pig vas deferens and that released from the tissue following stimulation of adrenergic nerves. The total tissue content was measured to be 1.6, 0.76, and 0.10 mumol/g of ATP, ADP, and AMP, respectively. However, adenosine could not be detected. Hypoxia caused a significant decrease in ATP content concomitant with an increase in adenosine content to 0.04 mumol/g. Following transmural electrical stimulation of the guniea pig vas deferens, the release of the following purine compounds was detected: ATP (0.106 nmol/g), ADP (0.242 nmol/g), AMP (0.035 nmol/g), and adenosine (0.454 nmol/g).

Acetaldehyde↗

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↗

Catecholamines in the vasculature of the rat and rabbit: dopamine, norepinephrine, epinephrine.

A highly sensitive radioenzymatic assay for the measurement of catecholamines in small blood vessels was applied to the measurement of the levels of norepinephrine (NE), dopamine (DA) and epinephrine (E). The results showed the presence of NE, E and DA in all segments of rat or rabbit vascular tissue analyzed. The predominant catecholamine in the vasculature from both species was NE, and the contents of E and DA were similar for most vessels. Unexpectedly large concentrations of E were associated with rabbit blood vessels.

Animals↗

Isolated brain microvessels: preparation, morphology, histamine and catecholamine contents.

A method for the rapid preparation of parenchymal microvessels from rat, rabbit and bovine brains is described. Light and electron microscopic examination of the isolated microvessels showed the smooth muscle and endothelial cells to be intact and substantially free of neutrophil contamination. The observation of 0.2 to 2.0 micron electron dense granules in the adventitial space associated with some of the isolated arteriolar elements and the identification of histamine in microvessel extracts is suggestive of the presence of mast cells in the microvessel preparations. Age-dependent changes in histamine content and an increased histamine content in microvessels from hypertensive rats were noted. Using a sensitive radioenzymatic assay, the catecholamine (CA) contents of microvessels isolated from cow, rat and rabbit were measured. The total CA contents of all microvessel preparations were small (< 0.35 microgram g-1) with norepinephrine being the predominant CA present. A large ratio of dopamine to norepinephrine was found in microvessels from rat and bovine brain. The possible origins of the CAs present in the isolated microvessels are discussed.

Animals↗

Uptake and O-methylation of isoprenaline in the rabbit ear artery.

Factors which influence uptake on O-methylation of 3H-isoprenaline (3HISO) by isolated segments of the rabbit ear artery were investigated. The tendency of the artery to accumulate unchanged amine was enhanced either when the O-methylation of ISO approached saturation at a high substrate concentration (6 mumol 1(-1) ISO), or when O-methylation was inhibited. Under these conditions, deoxycorticosterone acetate (DOCA) partially inhibited the accumulation of ISO. DOCA exerted a stronger inhibitory effect on O-methylation, but only at low ISO concentrations (0.2 and 0.8 mumol 1(-1)). The results are interpreted as evidence that (a)O-methylation in the intact artery is a saturable process which serves to limit the accumulation of 3HISO when the bathing concentration of the amine is low, and (b) DOCA exerts its effects by inhibiting extraneuronal uptake into the compartment possessing O-methylating activity. Analysis of the kinetics of efflux of 3HISO suggested that O-methylation was restricted to only one compartment, whereas unchanged ISO was accumulated within at least two compartments in addition to the extracellular compartment. Attention is drawn to a small but significant inhibitory effect of chronic sympathetic denervation on the accumulation, although not the O-methylation of ISO, raising the possibility that there may also be distribution of 3HISO within the sympathetic nerves.

Animals↗

Altered disposition of vascular catecholamines in hypertensive (DOCA-salt) rats.

The levels of norepinephrine (NE), dopamine (DA) and epinephrine (E) in the vasculature of hypertension (DOCA-SALT) and normotensive rats were determined by radioenzymatic assay. Significant decreases in the NE content of the mesenteric artery, renal artery and cardiac tissue from DOCA-Salt treated rats were found. In contrast the NE content of the inferior vena cava, abdominal aorta and mesenteric vein were not significantly decreased in the DOCA-Salt treated rats. There was no evidence of an altered disposition of DA and E in the vasculature of DOCA-Salt treated rats. The results of the study indicate that NE is selectively depleted in the cardiovascular system of this model of experimental hypertension and it is proposed that this property reflects different functional roles of individual elements of the vasculature in the DOCA-Salt hypertensive rat.

Animals↗

Adrenal origin of plasma catecholamines after decapitation: a study in normal and diabetic rats.

The concentrations of catecholamines and the activities of dopamine-beta-hydroxylase were measured in blood obtained from decapitated diabetic and aged-matched control rats. The activity of dopamine-beta-hydroxylase in blood from diabetic rats was much greater (5 fold) than that seen for control rats. For both diabetic and control rats, decapitation was accompanied by an increase in levels of adrenaline and noradrenaline with no change in the activity of plasma dopamine-beta-hydroxylase. The results are consistent with a predominantly adrenal origin of catecholamines and extra-adrenal origin of dopamine-beta-hydroxylase. The high activity of dopamine-beta-hydroxylase in diabetes indicates either an increased activity of the sympathetic nervous system or changes in dopamine-beta-hydroxylase turnover.

Adrenal Glands↗

Semi-automated catecholamine assay.

Three semi-automated procedures are described for the estimation of the catecholamine contents of urine, tissue and plasma samples. The three procedures are based on the fluorometric tri-hydroxyindole assay which has been modified for automatic analysis. These techniques offer several advantages over currently available assays in that they are more convenient, provide for faster analysis rate and give increased sensitivity. The results of the present studies in which the catecholamine contents of urine, tissue and plasma samples were determined using the semi-automated assay provided a range of values which was identical to that obtained using other methods.

Adrenal Glands↗

Endogenous histamine in rabbit thoracic aorta.

A sensitive automated assay was developed for the determination of histamine. The endogenous histamine content of intact rabbit thoracic aorta, and of its separated adventitial and medial layers was determined. The histamine content of the intact aorta was found to be only partially sensitive to compound 48/80. The isolated aorta accumulated labelled histamine against a concentration gradient. The uptake was abolished by cooling to 1 degree, but was unaffected by oxygen lack. The uptake process was sensitive to a variety of agents including extraneuronal catecholamine uptake inhibitors (deoxycorticosterone acetate, normetanephrine) as well as inhibitors of catecholamine and histamine metabolism (tranylcypromine, hydrallazine). The uptake was not affected by amodiaquin, a histamine N-methyl-transferase inhibitor, by the metabolites 1,4-methylhistamine or imidazole acetic acid, by compound 48/80 or by the basic amino acid arginine.

Animals↗