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J R Fozard

Publications and source records attributed to J R Fozard.

133 records · Page 8Linked to original sources
PubMedDate not supplied

Lack of a role for cardiac sympathetic nerves in the uptake and metabolism of 3H-5-hydroxytryptamine by isolated rabbit hearts.

Perfused rabbit hearts removed 3H-5-hydroxytryptamine (3H-5-HT) from a perfusion solution containing 2.6 ng/ml and a tissue-to-medium ratio of about 10 was achieved after a 55 min perfusion period. 12.4 +/- 1.0% of the cardiac total radioactivity consisted of metabolites and metabolites appeared in the venous effluent during the course of the perfusion. Pretreatment of animals with 6-hydroxydopamine reduced cardiac noradrenaline concentrations by 92%, abolished the histochemical fluorescence characteristic of noradrenaline in sympathetic nerves and abolished the mechanical response to sympathetic nerve stimulation. In these hearts, the removal of 3H-5-HT from the perfusion fluid and the accumulation of total radioactivity was normal. There was, however, a significant increase in the proportion of the total cardiac radioactivity which was present as metabolites. The results suggest that the cardiac sympathetic nerves are not the site of 3H-5-HT uptake when the concentration in the perfusion medium is low. By analogy with work in the lung, it may be the endothelial cells of the coronary microcirculation which are responsible.

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PubMedDate not supplied

Mechanism of the antihypertensive action of DL-alpha-monofluoromethyldopa: implications for the role of the sympathetic nervous system in maintenance of elevated blood pressure in spontaneously hypertensive rats.

We investigated the mechanism of the antihypertensive action of DL-alpha-monofluoromethyldopa (MFMD), an irreversible inhibitor of L-aromatic amino acid decarboxylase, in spontaneously hypertensive rats (SHR). MFMD, 25 mg/kg i.p. daily for 3 days, reduced mean arterial blood pressure by 47 +/- 11 mm Hg (n = 6; p less than 0.001). The effect was associated with marked attenuation of the responses to stimulation of the whole sympathetic outflow in pithed preparations and with substantial reductions in the norepinephrine concentrations of hearts and portal veins. Similar functional and biochemical deficits were produced in age-matched, Wistar--Kyoto, normotensive rats, but blood pressure in these animals fell only by an average of 8 +/- 4 mm Hg (n = 5; NS). Blood pressure of SHR, lowered by MFMD, was restored to pretreatment levels by infusion with dopamine (0.1 mg/kg/min for 5 min), and there was a concomitant return towards normal of both the peripheral sympathetic transmitter stores and the response to stimulation of the nerves supplying the cardiovascular system. Neither the dopamine nor the norepinephrine concentrations of the brain, depleted by treatment with MFMD, were altered following infusion of dopamine. These results provide direct evidence that attenuation of sympathetic function arising from depletion of the peripheral transmitter store is the mechanism by which MFMD lowers blood pressure in SHR. They further lend strong support to the view that hyperactivity of the sympathetic nervous system plays a primary role in the maintenance of the elevated blood pressure in the genetically hypertensive rat.

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PubMedDate not supplied

The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation of migraine?

The evidence for an involvement of 5-hydroxytryptamine (5-HT) and nitric oxide (NO) in the initiation of migraine is reviewed. Based on this, the following scenario is proposed. Endogenous 5-HT, arising perhaps from platelets but more likely from perivascular 5-HT-containing neurons in response to different types of "stress", would activate 5-HT2B/5-HT2C receptors on endothelial cells of the cerebral vasculature to release NO. Nitric oxide would, by directly activating sensory neurons, induce neurotransmitter release, plasma extravasation, pain and hyperalgesia. The result would be induction of the "sterile" inflammatory response, believed to be the key step in the development of migraine.

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