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Biomedical subjects

R E Purdy

Publications and source records attributed to R E Purdy.

At least 73 records · Page 4Linked to original sources
PubMed1984

The effects of steroid hormones on vascular tissue.

Results of clinical and experimental studies suggest that extrarenal actions of corticosteroid hormones must be involved in the overall effects of these steroids on the circulation. A dissociation between levels of mineralocorticoids and sodium balance or renal effects of steroid hormones is often observed in patients with primary or secondary forms of hypertension. Receptors for various steroids have been found in the peripheral circulation. Stimulation of these receptors probably leads to changes in the electrolyte content of the cell. In turn, these changes have a direct or indirect effect on the contractility of the vascular wall. The physiological importance of the vascular effects of steroids in human hypertension remains to be elucidated.

Animals↗
PubMed1984

Characterization of the alpha adrenergic receptor properties of rabbit ear artery and thoracic aorta.

The alpha adrenoceptor properties of the rabbit ear artery and thoracic aorta were assessed using isolated blood vessel rings mounted in tissue baths. ED50 values and dissociation constants for norepinephrine (NE), epinephrine (EPI), isoproterenol (ISO), methoxamine (MET) and clonidine (CLO) were determined by analysis of dose-response data with and without partial inactivation of alpha receptors by phenoxybenzamine. The order of affinity of these agonists for the alpha receptors of ear artery was CLO less than EPI = NE = MET much less than ISO, and that in aorta was EPI less than NE less than CLO less than MET less than ISO. Alpha receptor reserves were larger in ear artery than aorta by factors of 182, 17, 7, 3.8 and 2 for EPI, NE, ISO, MET and CLO, respectively. In contrast, the fraction of receptors occupied at threshold contractile response was larger in aorta than ear artery with every agonist studied except CLO. The maximal response to the partial agonist, CLO, expressed as a fraction of the maximal response to NE in each vessel, was nearly 1.8 times greater in ear artery than in aorta. It is concluded that the alpha receptors of rabbit ear artery are qualitatively different from those of the thoracic aorta. In addition, the larger receptor reserves, smaller fraction of receptors occupied at threshold and the larger maximal response of CLO in ear artery support the hypothesis that alpha receptor density in this vessel is greater than that in the aorta.

Animals↗
PubMed1983

Enhancement and prolongation of vascular smooth muscle contraction by aldosterone.

Isolated rings of rabbit thoracic aorta were mounted in tissue baths for the measurement of isometric tension development and desipramine was added to all baths to block neuronal uptake of catecholamines. When these vessels were contracted to a steady-state of 1.5-3.5 g with norepinephrine, the addition of 1, 10 and 100 microM aldosterone caused a further contraction of 0.09, 0.47 and 0.8 g, respectively. Vessels contracted with norepinephrine and exposed to aldosterone were also immersed in mineral oil to trap a finite amount of norepinephrine within the receptor compartment of the tissue and the rate of relaxation was measured. The time to relax 50% (t1/2) in the presence of 100 microM aldosterone was approximately 18 min, while that in the presence of either ethanol diluent or 10 microM aldosterone was 7 min. When maximally effective concentrations of aldosterone and deoxycorticosterone acetate were used, the increases in norepinephrine-induced contractions and relaxation t1/2 values caused by these agents were identical. Combining these agents did not produce additive effects. Aldosterone also increased contractions and t1/2 values in tissues contracted with epinephrine but not in those contracted with methoxamine or 5-hydroxytryptamine. These findings support the conclusion that aldosterone enhances and prolongs contraction by inhibiting the removal of catecholamines from the receptor compartment of vascular smooth muscle.

Aldosterone↗
PubMed1983

Qualitative and quantitative differences between the postsynaptic alpha adrenoceptors of rabbit ear artery and thoracic aorta.

The alpha adrenoceptor properties of the rabbit ear artery and thoracic aorta were assessed using isolated blood vessel rings mounted in tissue baths. Labetalol, an alpha and beta receptor antagonist, caused dose-dependent contractions in control, reserpinized and surgically denervated ear arteries. This contraction was inhibited by phentolamine and abolished by the irreversible alpha receptor antagonist, N,N'-bis-(O-methoxy-benzylaminohexyl) cystamine tetrahydrochloride. Thoracic aorta failed to respond to labetalol. Using labetalol as an antagonist against methoxamine, labetalol pA2 values were 7.4 +/- 0.3 (95% confidence interval) and 7.13 +/- 0.25 in ear artery and aorta, respectively. Thus, labetalol had the same affinity for the alpha receptors of these two vessels but was an alpha agonist only in the ear artery. Norepinephrine ED50 values and dissociation constants (KA) were determined by analysis of dose-response data with and without partial inactivation of alpha receptors by phenoxybenzamine. Ear artery and aorta norepinephrine ED50 values, 4.24 (2.24-8.03) X 10(-8) M and 2.48(1.64-3.76) X 10(-8) M, respectively, were not significantly different. In contrast, norepinephrine KA values differed by a factor of 32, 4.11 (3.02-5.60) X 10(-6) M and 1.29 (0.85-1.94) X 10(-7) M, respectively. Receptor reserves were also markedly different in these vessels. Thus, ED50 was achieved with 1% receptor occupancy in ear artery as compared to 16% receptor occupancy in aorta. It is concluded that the alpha receptors of ear artery and aorta are both qualitatively and quantitatively different.

Animals↗
PubMed1982

Vasoconstrictor effects of aldosterone in isolated vascular tissue.

Isolated rings of rabbit ear artery or thoracic aorta were prepared for the measurement of isometric contraction. Treatment of ear artery with 1 X 10(-4)M aldosterone had no effect. However, in ear artery pretreated with 1 X 10(-7)M desipramine to block the catecholamine neuronal uptake process, 1 X 10(-6), 1 X 10(-5) and 1 X 10(-4)M aldosterone elicited contractions of 0.16, 0.48 and 1.31 g, respectively. Phentolamine, 1 X 10(-7)M, an alpha adrenoceptor antagonist, both prevented and reversed the aldosterone-induced contractions. Desipramine-pretreated thoracic aortas were contracted to a steady-state of 1-2 g with norepinephrine and immersed in mineral oil to prevent diffusion of drugs from the tissue. Relaxation, which reflects the rate of tissue inactivation of norepinephrine, was markedly slowed by exposure of these tissues to either aldosterone, deoxycorticosterone acetate (an inhibitor of the catecholamine-extraneuronal uptake process) or the combination of these steroids prior to oil immersion. It is concluded that in the ear artery, endogenous norepinephrine was spontaneously released from intramural nerves and that aldosterone blocked the catecholamine extraneuronal uptake process within the muscle coat allowing the concentration of norepinephrine to increase well above the threshold for contraction.

Aldosterone↗
PubMed1982

The role of aldosterone in the response to treatment of primary hypertension.

The role of the renin-aldosterone axis in mediating responses to antihypertensive treatment was examined in patients with essential hypertension treated with propranolol (n=50) or chlorthalidone (n=50). Control plasma renin activity tended to be predictive of the response to treatment: it correlated with the diastolic blood pressure changes produced by both the renin-lowering agent, propranolol (r=-.43, P less than 0.001), and the diuretic, chlorthalidone (r= .48, P less than 0.001). However, when patients were divided into responders (fall in diastolic blood pressure of greater than 10%) and non-responders, the treatment-induced changes in aldosterone excretion rate appeared to be more important than the changes in renin in determining outcome. During propranolol there was no difference between the renin changes in the responders (n=21) and the non-responders (n=29), but aldosterone fell significantly more (P less than 0.025) in the responders than in the non-responders. Similarly, renin changes during chlorthalidone were not markedly different between the two groups, but the increase in aldosterone excretion in the non-responders was significantly greater (P less than 0.001) than in the responders (n=25). Thus, regardless of the treatment used, responders were characterized by having lower levels of aldosterone during therapy than non-responders. This possible role for aldosterone in influencing blood pressure changes was not related to clinically measurable effects on fluid and electrolyte balance; it has been conjectured that this pressor effect of aldosterone could reflect a direct action in the peripheral circulation.

Adult↗
PubMed1981

Clofibrate and vascular smooth muscle: actions on rabbit aorta preparations.

Clofibrate (Atromid-S) has been found to inhibit the contractility of isolated rabbit aortic muscle rings produced by exposure to either norepinephrine, histamine or angiotensin. The inhibitory effect of clofibrate is seen optimally in Krebs medium containing low, 5 X 10-5 M, calcium but is not found in medium containing 2.5 X 10-3 M calcium. In contrast, clofibrate does not inhibit contractions triggered by depolarizing concentrations of K+, in either low or normal Ca medium. Since only receptor-mediated contractions are inhibited, it is suggested that the actions of clofibrate in aorta influence an event common to receptor-linked contractions, possibly by interfering with the utilization of membrane-bound calcium.

Angiotensin II↗
PubMed1981

Receptors for 5-hydroxytryptamine in rabbit isolated ear artery and aorta.

The effects of N,N'-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC), 2-brom-d-lysergic acid diethylamide (BOL) and prazosin on 5-hydroxytryptamine (5-HT) dose-response curves in rabbit ear artery and thoracic aorta were determined. BHC, an irreversible alpha-adrenoceptor antagonist, and prazosin had no substantial effect while BOL shifted the 5-HT dose-response curve to the right in aorta. BHC shifted the curve to the right and reduced maximal response to 5-HT in ear artery. BOL shifted the curve to the right only above 10(-6) M 5-HT in control, but at all concentrations studied in BHC-pretreated ear arteries. In vitro denervation of the ear artery with 6-hydroxydopamine did not significantly alter the 5-HT dose-response curve, nor the effect of BHC on that curve. On the other hand, desipramine decreased the contractile response to high concentrations of 5-HT in non-denervated ear arteries. Prazosin increased the 5-HT threshold and slope of the curve in the ED50 region, but had no inhibitory effect on contractile responses above 3 x 10(-7) M 5-HT or on maximal response. It is concluded that 5-HT acts exclusively on 5-HT receptors in aorta, but on both alpha-adrenergic and 5-HT receptors in ear artery. 5-HT also possesses a small indirect sympathomimetic action at high concentrations in the ear artery. Prazosin has no effect on 5-HT receptors in either vessel and blocks the alpha-adrenoceptor stimulation by 5-HT in ear artery.

Animals↗
PubMed1981

Effects of reserpinization, surgical denervation and in vitro chemical denervation with 6-hydroxydopamine on the contractile response of isolated rabbit ear artery to propranolol.

The contractile effect of propranolol in isolated rabbit ear artery was assessed in reserpinized and in surgically and chemically denervated blood vessels. Reserpinization and surgical denervation either had no effect on or enhanced the ear artery contractile response to 10(-6) to 10(-4) M propranolol. In contrast, the contractile response to propranolol was nearly abolished after denervation of the ear artery in vitro with 6-hydroxydopamine (6-OHDA). Dose-response curves to norepinephrine were shifted to the left by factors of 4.9 in 6-OHDA denervated ear arteries and 15.6 in untreated arteries in the presence of 10(-7) M desipramine. The diluent for 6-OHDA shifted both the norepinephrine and propranolol dose-response curves to the right. It is proposed that propranolol caused a contractile response in ear artery by an action on the postsynaptic tissues of this vessel. 6-OHDA denervation caused nonspecific desensitization in rabbit ear artery leading to the loss of response of this vessel to propranolol.

Animals↗
PubMed1979

Acquisition deficits induced by sodium nitrite in rats and mice.

Graded doses of sodium nitrite were administered shortly before or immediately after a single training trial in an inhibitory avoidance task. A retention test was given at 24 h (rats) or 72 h (mice) after training. The results indicate that sodium nitrite impairs acquisition of an inhibitory avoidance response in rats and mice. Retention was impaired with doses lower than those required for producing hypoxic effects, as measured by the EEG, methemoglobin levels in the blood, blood pressure, and heart rate. Since hypoxia was not involved, it is likely that the effects were mediated by some direct action of sodium nitrite on the CNS.

Amnesia↗
PubMed1978

The evaluation of cardiovascular drugs in the anaesthetized, unrestrained rat.

A method is reported which allows continuous long-term drug administration and simultaneous blood pressure measurement in the unanaesthetized unrestrained rat. The external jugular vein and abdominal aorta were cannulated and the opposite ends of the cannulae were passed subcutaneously and exteriorized at the back of the head. They were then passed through a spring attached at the lower end to the skull and, at the upper end, to a counter-weighted cantilever. In rats so prepared, infusion of angiotensin amide 200 ng kg-1 min-1 caused a rise of blood pressure which lasted the 48 h infusion period. Heart rate decreased initially but recovered within 6 h. Angiotensin amde 30 ng kg-1 min-1, infused up to seven days, was without effect on blood pressure or heart rate, and both doses of angiotensin amide failed to alter cardiac catecholamine turnover. Hydralazine, mecamylamine and clonidine reduced blood pressure to 63, 62 and 84% of control respectively while clonidine induced a transient increase before its depressor effect. Heart rate was increased by hydralazine to 138%, and decrease by clonidine to 74% of control, and was unaffected by mecamylamine. The magnitude of pressor response to noradrenaline, tyramine and angiotensin was reduced by hydralazine and increased by mecamylamine. Clonidine increased the pressor response to angiotensin but had no effect on that to noradrenaline or tyramine.

Angiotensin II↗
PubMed1977

Effect of carbamazepine on the in vitro uptake and release of norepinephrine in adrenergic nerves of rabbit aorta and in whole brain synaptosomes.

The effects of carbamazepine, in vitro, on adrenergic neuronal and whole brain synaptosomal uptake and release of tritiated norepinephrine (3H-NE) were assessed. At 10(-4) M, carbamazepine inhibited 3H-NE uptake by 22% in rabbit thoracic aorta and in brain synaptosomes. At the same concentration, carbamazepine inhibited stimulation-induced release of 3H-NE by 42.6% and inhibited isometric contraction in rabbit ear artery helical strips by 31.6%. At 10(-5) M, carbamazepine exhibited a 17.6% inhibition of 3H-NE uptake in brain synaptosomes in the absence of effects on transmitter release. Cocaine, 10(-4) M, and imipramine, 10(-4) M, inhibited uptake by 88% and 85%, respectively, in aorta, and cocaine, 10(-4) M, inhibited synaptosomal uptake by 67.7%. Since antiepileptic blood levels of carbamazepine range between 1.3 and 3.0 X 10(-5) M, it was concluded that the observed effects of carbamazepine are insufficient to account for the anticonvulsant action of the drug. However, the blockade of 3H-NE uptake by brain synaptosomes at 10(-5) M serves to explain the recently described analeptic activity of this agent.

Adrenergic Fibers↗