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S J Godwin

Publications and source records attributed to S J Godwin.

9 recordsLinked to original sources
PubMed2000

Effects of central infusion of ANG II and losartan on the cardiac baroreflex in rabbits.

The effect of chronic activation or inhibition of central ANG II receptors on cardiac baroreflex function in conscious normotensive rabbits was examined. Animals received a fourth ventricular (4V) infusion of ANG II (30 and 100 ng/h), losartan (3 and 30 microg/h), or Ringer solution (2 microl/h) for 2 wk. After 1 and 2 wk, ANG II (100 ng/h) decreased cardiac baroreflex gain by 20 and 37%, respectively (P = 0.015), whereas losartan (30 microg/h) increased baroreflex gain by 24 and 58%, respectively (P = 0.02). Within 1 wk of the end of the infusions, cardiac baroreflex gain had returned to control. Ringer solution or the lower doses of ANG II or losartan did not modify the cardiac baroreflex function. Blood pressure and heart rate were not altered by any treatment, nor was their variability affected. These data demonstrate a novel long-term modulation of cardiac baroreflexes by endogenous ANG II that is independent of blood pressure level.

Angiotensin II↗
PubMed1998

Comparison of the baroreceptor-heart rate reflex effects of moxonidine, rilmenidine and clonidine in conscious rabbits.

In 10 conscious rabbits, the baroreceptor-heart rate (HR) reflex effects of centrally acting antihypertensive agents with high affinity for imidazoline receptors (IRs), moxonidine and rilmenidine, were compared with clonidine which acts predominantly via central alpha2-adrenoceptors. Dose regimens were chosen to give similar hypotension (-17+/-1 mm Hg) and bradycardia (-27+/-2 b/min) for all three agents given into the fourth ventricle. Baroreceptor-HR reflex curves were assessed by i.v. drug induced changes in blood pressure. With all treatments, the baroreflex curves with both vagal and sympathetic effectors intact were shifted to the left, corresponding to the hypotension, and the bradycardia plateau was reduced. Rilmenidine and moxonidine also reduced the upper plateau such that the curves were shifted parallel down the HR scale with no change in the HR range. By contrast, clonidine only decreased the lower plateau, and thus increased HR range (+19+/-6%). Moxonidine, but not rilmenidine, reduced the baroreflex gain by reducing the curvature. Clonidine also decreased curvature but this did not result in a reduction in gain as it was offset by the increase in HR range. The gain and range of the cardiac sympathetic component, as assessed after vagal blockade, was reduced by rilmenidine by 53 and 40% respectively, but was not affected by the other agents. The calculated vagal component of the curves showed that all agents produced a greater vagal bradycardia in response to a rise in pressure and that both rilmenidine and clonidine increased vagal HR range. The present study results show that many of the baroreflex effects of clonidine, such as facilitating cardiac vagal responses, are shared by the second generation agent rilmenidine, suggesting that they are primarily due to alpha2-adrenoceptor activation. In addition, the inhibition of the sympathetic component of the baroreflex, observed with rilmenidine, and not clonidine suggests that this effect may involve IRs. By contrast moxonidine, the most specific agent for I1 receptors, produces mainly a baroreflex independent inhibition of cardiac sympathetic activity with little effect on vagal activity.

Adrenergic alpha-Agonists↗
PubMed1998

Role of central catecholaminergic pathways in the actions of endogenous ANG II on sympathetic reflexes.

In the present study, we examined the effect of blockade of the brain stem renin-angiotensin system on renal sympathetic baroreflexes and chemoreflexes in conscious rabbits and examined the role of central catecholaminergic pathways in these responses. Eleven rabbits underwent preliminary surgical instrumentation and pretreatment with central 6-hydroxydopamine (6-OHDA, 500 micrograms/kg) or ascorbic acid 6 wk before the commencement of the experiments. Baroreflex curves were determined under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after central administration of either Ringer solution, the ANG II receptor antagonist losartan (10 micrograms), or the angiotensin-converting enzyme inhibitor enalaprilat (500 ng) on separate days. Losartan increased the upper plateau and the range of the mean arterial pressure (MAP)-renal sympathetic nerve activity (RSNA) curve (79 and 78%, respectively) in intact rabbits, whereas this effect was not observed in 6-OHDA-pretreated rabbits. Hypoxia elicited an increase in resting RSNA (111% in intact rabbits and 74% in 6-OHDA-injected rabbits) and elevated the upper plateau of the RSNA-MAP curve in both groups (89% in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan and enalaprilat increased the RSNA upper plateau in intact rabbits but had no effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rate baroreflex curves were observed. Thus the effect of losartan to increase RSNA, particularly during hypoxia and baroreceptor unloading, being abolished by central noradrenergic depletion suggests that the endogenous ANG II which normally causes an inhibition of renal sympathetic motoneurons is dependent on the integrity of central catecholaminergic pathways.

Angiotensin II↗
PubMed1997

Central cardiovascular actions of agmatine, a putative clonidine-displacing substance, in conscious rabbits.

Agmatine, an endogenous clonidine-displacing substance, has been shown to have an affinity for both alpha 2-adrenoceptors and imidazoline receptors (IR). In conscious rabbits, we have examined the cardiovascular effects of agmatine and its interaction with clonidine, a presumed agonist and 2-methoxyidazoxan, an antagonist at alpha 2-adrenoceptors. We have also examined the effect of agmatine on agents having high affinity for I1-imidazoline receptors namely moxonidine (agonist) and efaroxan (antagonist). Initial dose-response studies showed that agmatine administered in low doses (0.01-10 micrograms/kg) into the fourth ventricle did not change mean arterial pressure but did produce a dose-dependent bradycardia (maximum -16 +/- 3 beats/min). A higher dose of 100 micrograms/kg produced an adverse reaction in the conscious animals accompanied by a marked increase in mean arterial pressure and a reversal of the bradycardia. This is in contrast to the effects of fourth ventricular clonidine and moxonidine, which caused a dose-dependent fall in both mean arterial pressure and heart rate. Agmatine when administered at the highest well-tolerated dose of 10 micrograms/kg did not further alter the clonidine-induced hypotension but produced a greater bradycardia (-12 +/- 4 beats/min clonidine; -29 +/- 4 beats/min clonidine plus agmatine; p < 0.05). Similarly, the hypotension induced by moxonidine was not altered by agmatine but heart rate was reduced after the addition of agmatine (p < 0.01). Efaroxan and 2-methoxy-idazoxan, at doses which produced no effects when given alone, similarly reversed the fall in heart rate elicited by agmatine and caused a small but significant rise in mean arterial pressure. We have previously shown that the doses of these antagonists used in this study produce an equal reversal of the bradycardia induced by fourth ventricular alpha-methyldopa (alpha 2-adrenoceptor agonist) and clonidine and hence have similar alpha 2-adrenoceptor blocking effects. Our results show that agmatine produces bradycardia as does moxonidine and clonidine but does not mimic or block the hypotensive responses to these agents. These findings do not support the hypothesis that agmatine is an endogenous ligand for IR. However, the bradycardia induced by agmatine may be mediated via alpha 2-adrenoceptors since it was equally blocked by efaroxan and 2-methoxy-idazoxan. Thus while alpha 2-adrenoceptor actions of agmatine on heart rate are evident at relatively low doses, the reason for the lack of alpha 2-adrenoceptor mediated hypotension is not known.

Adrenergic alpha-Agonists↗
PubMed1996

Medullary neurons activated by angiotensin II in the conscious rabbit.

Previous studies have shown that angiotensin II (Ang II) can activate cardiovascular neurons within the medulla oblongata via an action on specific receptors. The purpose of this study was to determine the distribution of neurons within the medulla activated by infusion of Ang II into the fourth ventricle of conscious rabbits, using the expression of Fos, the protein product of the immediate early gene c-fos as a marker of neuronal activation. Experiments were done in both intact and barodenervated animals. In comparison with a control group infused with Ringer's solution alone, in both intact and barodenervated animals, fourth ventricular infusion of Ang II (4 to 8 pmol/min) induced a significant increase in the number of Fos-positive neurons in the nucleus of the solitary tract and in the rostral, intermediate, and caudal parts of the ventrolateral medulla. Double-labeling for Fos and tyrosine hydroxylase immunoreactivity showed that 50% to 75% of Fos-positive cells in the rostral, intermediate, and caudal ventrolateral medulla and 30% to 40% of Fos-positive cells in the nucleus of the solitary tract were also positive for tyrosine hydroxylase in both intact and barodenervated animals. The distribution of Fos-positive neurons corresponded very closely to the location of Ang II receptor binding sites as previously determined in the rabbit. The results indicate that medullary neurons activated by Ang II are located in discrete regions within the nucleus of the solitary tract and ventrolateral medulla and include, in all of these regions, both catecholamine and noncatecholamine neurons.

Angiotensin II↗
PubMedDate not supplied

Effect of central endogenous angiotensin II on sympathetic activation induced by hypoxia.

This study examined the possible contribution of the brain renin-angiotensin system on the sympathetic activation induced by hypoxia in conscious rabbits. Blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after fourth ventricular administration of either losartan (10 micrograms in 25 microliters), enalaprilat (500 ng in 25 microliters) or Ringer's (25 microliters). Hypoxia increased the RSNA by 113% and slightly decreased HR without changing BP. It also increased the variability of BP or HR in the 0.2-0.4 Hz frequency domain. Losartan and enalaprilat did not change the resting BP or HR but elevated the RSNA increase seen during hypoxia. Our results suggest that central angiotensin is involved in mediating response to chemoreceptor activation.

Angiotensin II↗