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Biomedical subjects

G S Stokes

Publications and source records attributed to G S Stokes.

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

Studies in the rat on the haemodynamic overshoot response to withdrawal of guanfacine or clonidine treatment.

1. Normal rats were injected intramuscularly twice daily for either 3 days or 3 weeks with guanfacine (0.1 or 1.0 mg/kg), clonidine (0.01 or 0.1 mg/kg) or 0.9% saline. All were anaesthetized at various times before or after the last injection, and their arterial pressures and heart rates were monitored via a carotid artery catheter. 2. Overshoots in systolic and diastolic pressure and heart rate, reaching peak values as soon as 16 h after the last injection, occurred in all rats withdrawn from guanfacine or clonidine treatment, but in no control rats. 3. Post-withdrawal blood pressures and heart rates of rats which had received the low dose of guanfacine or clonidine were as great as those of rats which had received the ten-fold greater dosage. Moreover, withdrawal responses were as great in rats which had been treated for only 3 days as in those treated for 3 weeks. 4. The dosages and duration of treatments used in these experiments thus did not influence the magnitude of the haemodynamic overshoots provoked by withdrawal of guanfacine or clonidine. However, all groups of rats from which guanfacine was withheld exhibited significantly greater peak overshoots in systolic and diastolic pressure than did those withdrawn from clonidine treatment.

Animals↗
PubMedDate not supplied

Profile of a new prazosin congener, BL-5111A. Studies in the rat.

1. The effects on blood pressure and heart rate of prazosin and a structurally-related congener, BL-5111A, were compared in conscious and anaesthetized rats. 2. Both agents induced dose-related falls in systolic and diastolic blood pressure, with relatively little effect on heart rate. The hypotensive potency of prazosin was twenty-fold greater than that of BL-5111A. 3. The hypotensive activity of prazosin was abolished by pretreatment with the ganglionic blocking agent, pentolinium, or the alpha-adenoceptor blocking agent, phentolamine, whereas BL-5111A retained significant hypotensive activity (up to 28%) after either pretreatment. 4. Both prazosin and BL-5111A attenuated pressor responses to noradrenaline, and reversed the responses to adrenaline, prazosin being, in this respect, 6 times more potent than BL-5111A. There was a highly significant relationship between the alpha-adrenoceptor blocking activity of either agents and its hypotensive effect. 5. BL-5111A differed from prazosin in possessing, in addition to its predominant alpha-adrenoceptor blocking action, a minor component of action attributable to direct vasodilatation.

Anesthesia↗
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Responsiveness of hypertensive subjects to prazosin.

1. Plasma drug levels and blood pressure changes produced by a single 2 mg oral dose of prazosin were determined in nine hypertensive patients. 2. Regression analysis showed that there was a high degree of correlation between plasma prazosin concentration and change in mean blood pressure. 3. There were marked differences between patients in their responsiveness to prazosin.

Blood Pressure↗
PubMedDate not supplied

Blood pressure and its relationship to low levels of alcohol consumption.

The association between average weekly alcohol consumption and blood pressure was studied in relation to age, adiposity and smoking in 13 535 men and 7385 women. There was a progressive increase in blood pressure with increasing alcohol consumption, even at low levels of consumption.

Alcohol Drinking↗
PubMedDate not supplied

Vascular smooth muscle serotonin and alpha-adrenoceptors.

Rat isolated perfused tail arteries were used to investigate interactions between serotonin receptors and alpha-adrenoceptors. Ketanserin was shown to be a potent serotonin antagonist (pA2 = 9.17, s.e.m. = 0.06, n = 6) which also antagonized phenylephrine (pA2 = 7.47, s.e.m. = 0.10, n = 4) and noradrenaline (pA2 = 7.55, s.e.m. = 0.14, n = 6). Ketanserin reduced the maximal response to serotonin but not to phenylephrine or noradrenaline. Prazosin antagonized phenylephrine (pA2 = 9.60, s.e.m. = 0.12, n = 5) and noradrenaline (pA2 = 9.14, s.e.m. = 0.11, n = 6) and had no effect on maximal responses. Prazosin reduced the maximal response to serotonin but did not displace the dose-response curve. These results are interpreted to indicate the existence of separate, but overlapping, serotonin and alpha-adrenoceptors.

Animals↗
PubMedDate not supplied

Erythrocyte cation fluxes in normal and hypertensive human subjects.

Intracellular cation concentrations ([Na]i, [K]i) and influxes of 22Na and 86Rb were determined in the erythrocytes of hypertensive and control groups of subjects. In both groups [Na]i showed a positive correlation with frusemide-resistant Na influx and was inversely correlated with ouabain-sensitive Rb influx, whereas [K]i was inversely correlated with frusemide-sensitive Na influx (FSNaI). No significant differences between groups were found in [Na]i, [K]i or frusemide-resistant Na influx. FSNaI was greater in males than females. FSNaI was slightly greater (P less than 0.06) in the hypertensive group, but the significance of the difference diminished with sex-matching. Ouabain-sensitive Rb influx was increased in the hypertensive group.

Adult↗
PubMedDate not supplied

Studies on the mechanism of action of the hypotensive effect of ketanserin.

Ketanserin, 0.01-3.0 mg/kg i.v., was found to cause a dose-related fall in blood pressure in anaesthetized rats. However, these decreases were only significant after 1 and 3 mg/kg doses. Subsequent administration of prazosin, 0.2 mg/kg i.v., had no significant effect on blood pressure. In the presence of ketanserin 3 mg/kg, plus prazosin 0.2 mg/kg, adenosine caused a significant dose-dependent fall in blood pressure in anaesthetized rats. Methysergide, 1 mg/kg i.v., significantly attenuated the blood pressure responses to serotonin in anaesthetized rats whereas ketanserin (1 and 3 mg/kg) had no overall effect on serotonin responses. Ketanserin, 1 and 3 mg/kg i.v., was found to antagonize the pressor effects of phenylephrine and reverse the pressor effects of adrenaline in anaesthetized rats. Responses to angiotensin II were not significantly affected by ketanserin. These results suggest that ketanserin lowers blood pressure in anaesthetized rats by blockade of alpha-adrenoceptors.

Anesthesia↗
PubMedDate not supplied

Serotonin (5HT) and its antagonists: involvement in the cardiovascular system.

The cardiovascular actions of serotonin and its antagonists are reviewed with a view to clarifying whether serotonin has a role in blood pressure control through actions on the peripheral vasculature. Serotonin has complex actions in the heart and vasculature but none of these actions is completely understood. There is no doubt, however, that serotonin has extensive interactions with the sympathetic nervous system. The nature of the serotonin receptor is also discussed. There is extensive evidence that more than one type of serotonin receptor exists. Biochemical studies in brain homogenates have delineated two sub-populations of serotonin receptors, named 5HT1 and 5HT2. It is not clear whether the same receptor types exist in the vasculature but various actions of serotonin on the vasculature have tentatively been ascribed to actions on 5HT1- and 5HT2-type receptors. It is clear that there is some functional overlap between serotonin-receptors and alpha-adrenoceptors. The mechanism by which this overlap could occur is unknown although we suggest it may result from a physical overlap of serotonin receptors and alpha-adrenoceptors. Compounds which antagonize serotonin have provided the means for investigating serotonin receptors but have not clarified the role of serotonin in blood pressure control; certainly they have comparatively little effect on blood pressure and this may simply reflect the lack of free circulating serotonin. In animal studies the new serotonin antagonist ketanserin appears to lower blood pressure via alpha-adrenoceptor blockade.

Animals↗
PubMedDate not supplied

Investigations into the nature of alpha 2-adrenoceptors in rat tail arteries.

In rat isolated perfused tail arteries, dose-response curves were established for the vasopressor effects of phenylephrine (alpha 1-adrenoceptor agonist), clonidine (alpha 1- and alpha 2-adrenoceptor agonist), clonidine in the presence of 10(-7) mol/l prazosin (alpha 2-agonist), and BHT-920 (alpha 2-agonist). The ED50 values were: phenylephrine 1.85 X 10(-10) mol; clonidine 6.3 X 10(-10) mol; clonidine + prazosin 3.2 X 10(-6) mol; BHT-920 6.1 X 10(-6) mol. The arterial reactivity to BHT-920 was stable only after 4-5 h of perfusion. Responses to BHT-920 were not antagonized by yohimbine (alpha 2-adrenoceptor antagonist) but were antagonized by low concentrations of prazosin (alpha 1-adrenoceptor antagonist). These data constitute conflicting evidence regarding the existence of alpha 2-adrenoceptors in rat tail arteries. The data are consistent with the proposal that there are two recognition sites on alpha 1-adrenoceptors; phenylephrine and BHT-920 may stimulate different sites on alpha 1-adrenoceptors.

Animals↗