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Biomedical subjects

B F Robinson

Publications and source records attributed to B F Robinson.

At least 37 records · Page 2Linked to original sources
PubMed1988

Is the increased responsiveness to verapamil in the forearm resistance vessels of patients with hypertension a consequence of structural change?

A mathematical model has been developed that relates wall tension in resistance vessels to changes in both distending pressure and flow; the effect of alterations in wall: lumen ratio is taken into account. The model indicates that increased autoregulatory activity in the forearm circulation of patients with primary hypertension could result from an increased response of the vascular smooth muscle to increased intraluminal pressure, but it could be accounted for by an increase in wall:lumen ratio from about 0.2 to 0.3. When the effect of the same increase in wall:lumen ratio on response to dilator agents is examined, it appears that the enhanced response to verapamil could be accounted for by structural change and there is no need to postulate a functional change. If this view is correct, however, it becomes necessary to assume a reduced response of the vascular smooth muscle to sodium nitroprusside in patients with hypertension if the unchanged dilator effect of this drug is to be explained.

Dose-Response Relationship, Drug↗
PubMed1985

Functional differences in blood vessels determined from studies with calcium-channel blockers. Functional changes in forearm resistance vessels of men with primary hypertension.

Vascular smooth muscle is activated through 2 major systems. One, which can be inhibited by calcium-entry blocking agents, involves the influx of calcium through potential-sensitive channels. The other, which can be inhibited by sodium nitroprusside, involves the entry of calcium through agonist-controlled channels and probably its mobilization from within the cell as well. Human veins, muscular arteries and resistance vessels show differing patterns of response to agents that selectively inhibit the 2 activation systems. The responses indicate that physiologic contractions of cutaneous veins and muscular arteries depend on the agonist-controlled system; contractions of veins induced by high concentrations of potassium depend on the potential-sensitive system as, probably, does local spasm in arteries. The tone of resistance vessels depends on a balance between the potential-sensitive and agonist-controlled systems. The forearm resistance vessels of men with primary hypertension respond to verapamil with larger-than-normal dilatation compared with that induced by nitroprusside. This is interpreted as showing an increased contribution to resistance vessel tone from the potential-sensitive system. This functional abnormality does not depend on the inhibition of sodium pump activity that is known to occur in hypertension, because it cannot be reproduced by local infusion of ouabain. It probably results from a primary disorder of calcium handling by the cell membrane.

Calcium Channel Blockers↗
PubMed1985

Calcium-entry blocking agents in the treatment of systemic hypertension.

Calcium-entry blocking agents resemble established dilators such as diazoxide, minoxidil and hydralazine in that they act predominantly on the arterial resistance vessels and have little or no effect upon the veins. They have therefore been evaluated in the treatment of hypertension. Controlled studies have shown that verapamil and nifedipine are effective in decreasing blood pressure when given as sole agents. The antihypertensive effect of nifedipine is additive with that of a beta blocker, and nifedipine is also effective when given as a "third step" agent in combination with a beta blocker (or alpha methyldopa) and a diuretic. In contrast to other directly acting dilators, nifedipine causes, at most, only moderate stimulation of renin secretion and verapamil does not increase renin release at all; neither drug induces sodium retention. Both verapamil and nifedipine produce a moderate incidence of unwanted effects; these are mostly subjective in nature, but verapamil may cause constipation that is occasionally severe and nifedipine sometimes causes ankle swelling. Calcium-entry blockers should be considered as initial therapy when some contraindication exists to the use of other standard drugs. Nifedipine appears preferable to hydralazine for use in combination with a beta blocker and a diuretic: it is at least as effective as hydralazine and has a lower incidence of serious adverse effects.

Adrenergic beta-Antagonists↗
PubMed1984

The dilator response to K+ is reduced in the forearm resistance vessels of men with primary hypertension.

The dilator response to local infusion of K+ has been assessed in the forearm resistance vessels of 17 men with primary hypertension and 11 controls, by using a standard plethysmographic method. The response to infusion of K+ at 0.1 mmol/min was smaller in the patients with hypertension than in the normal controls (P less than 0.03). The results are consistent with the view that the activity of the sodium pump is depressed in the resistance vessels of patients with hypertension, but they yield no evidence as to whether or not this abnormality contributes to the elevation of the peripheral resistance.

Adult↗
PubMed1984

Effect of small increments in plasma calcium concentration on the responsiveness of forearm resistance vessels to verapamil in normal subjects.

The effect of a small increase in local plasma calcium concentration on the responsiveness of the forearm resistance vessels to verapamil has been examined in normal subjects, by using a plethysmographic method with infusion of calcium and other agents into the brachial artery. Infusion of calcium at a rate which increased the concentration in forearm venous blood by about 0.5 mmol/l caused basal blood flow to fall by 19% and the dilator response to verapamil to fall by 35% (n = 8; P less than 0.02). When, after 46 min, the infusion of calcium was discontinued, the dilator response to verapamil increased to reach a level 53% higher than the initial control (n = 8; P less than 0.02). Infusion of calcium had no effect on the dilator response to sodium nitroprusside. Infusion of noradrenaline at a rate which caused a greater reduction in basal flow than that induced by calcium had no effect on the response to verapamil. It is concluded that the dilator response to verapamil, which is thought to reflect activity of the potential operated system for calcium entry, is selectively depressed by a small elevation of plasma calcium concentration, but subsequently becomes elevated. These findings point to an important role for calcium in the regulation of membrane function in the resistance vessels and support the view that altered calcium handling may contribute to the development of primary hypertension.

Adult↗
PubMed1984

Small increments in plasma calcium concentration reduce the responsiveness of forearm resistance vessels to verapamil in men with primary hypertension.

The effect on the forearm resistance vessels of small increases in the local plasma concentration of calcium and magnesium has been examined in 20 men with primary hypertension. Studies were carried out by a standard plethysmographic method with infusion of drugs into the brachial artery. Infusion of calcium at 10 mumol/min into the forearm caused basal blood flow to fall by 9% (n = 17;0.1 greater than P greater than 0.05) and the dilator response to verapamil to fall by 28% (P less than 0.005). Infusion of magnesium at the same rate caused basal blood flow to rise by 22% (n = 12; P less than 0.05), but the dilator response to verapamil was not significantly changed. The response of the resistance vessels to verapamil is known to be enhanced in patients with hypertension, and the results show that this response is attenuated by a small increase in the local calcium concentration. The findings are consistent with the view that altered handling of calcium by the cell membrane contributes to the functional abnormality of the hypertensive resistance vessel.

Adult↗
PubMed1983

Differences in blood vessels between species: relation to differences in blood vessels of varying type within the same species.

1. Major differences in physiological and pharmacological responsiveness may be observed between blood vessels that differ either in anatomical type or in that they serve different organs or tissues. 2. The intrinsic properties of the vascular smooth muscle appears to differ little between species. No important differences in noradrenergic innervation have been observed, but major differences may exist in neural dilator systems. A few differences have been demonstrated that can be attributed to variations in the receptor population. No clear differences in local humoral mechanisms are known. There is, however, an insufficient number of strictly comparable studies in different species and it is likely that more differences will be found as our knowledge of vascular responsiveness is extended.

Animals↗
PubMed1983

Effect of local infusion of ouabain on human forearm vascular resistance and on response to potassium, verapamil and sodium nitroprusside.

The effect of local infusion of ouabain into the forearm vascular bed has been examined in 15 normotensive male volunteers in an attempt to define the nature of the functional abnormalities of the resistance vessels in primary hypertension. Ouabain and other drugs were infused into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography. Infusion of ouabain at 2 micrograms/min for 1 h caused a 26% reduction in forearm blood flow with a small rise in systemic arterial pressure; the increase in vascular resistance was unaffected by prior treatment with phentolamine. After infusion of ouabain the dilator response to potassium was reduced by 33% but the responses to verapamil and sodium nitroprusside were unchanged. The results show that acute depression of sodium pump activity by ouabain reproduces the increased resting resistance and impaired response to potassium that are seen in hypertension. It does not reproduce the relative enhancement of responsiveness to verapamil that is also observed in the resistance vessels of patients with hypertension and this abnormality must have some other cause.

Adult↗
PubMed1983

Effect of treatment with chlorthalidone and atenolol on response to dilator agents in the forearm resistance vessels of men with primary hypertension.

The forearm resistance vessels of men with primary hypertension respond to verapamil with a greater than normal dilatation relative to that induced by sodium nitroprusside. We have examined the effect on this functional abnormality of treatment with chlorthalidone (50 mg daily in 16 patients) and atenolol (100 mg daily in eight patients and 200 mg daily in two). The responsiveness of the forearm resistance vessels to local intra-arterial infusion of verapamil and sodium nitroprusside was assessed before treatment and again after a minimum of 1 month of drug therapy. Forearm blood flow was measured by venous occlusion plethysmography. Chlorthalidone induced significant reductions in calculated mean arterial pressure, which fell from 135 +/- 4 to 117 +/- 4 mm Hg, and the dilator response to verapamil at 5 micrograms/min, which was reduced from 2.4 +/- 0.2 to 1.5 +/- 0.2 ml min-1 100 ml-1 forearm; the response to sodium nitroprusside at 3.2 micrograms/min was not significantly changed. Atenolol induced significant reductions in mean arterial pressure, which fell from 134 +/- 6 to 123 +/- 6 mm Hg, heart rate which fell from 72 +/- 3 to 55 +/- 2 beats/min, and response to verapamil at 5 micrograms/min which fell from 2.7 +/- 0.2 to 2.1 +/- 0.2 ml min-1 100 ml-1 forearm; the response to sodium nitroprusside was not significantly changed. Both drugs caused reversion towards normal of the relative enhancement of responsiveness to verapamil that was present before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The response of forearm resistance vessels to dilator agents in patients with primary hypertension: use of nifedipine in long term therapy.

Local infusion of verapamil induced a significantly greater dilatation in the forearm resistance vessels of men with primary hypertension than that observed in a control group of men with normal arterial pressure; the response to sodium nitroprusside, however, was reduced. These findings indicate an abnormality in the mechanisms by which resistance vessel tone is maintained in patients with raised arterial pressure and they suggest that calcium channel blockers may be particularly suited for use as arteriolar dilators in hypertension. In an open trial in patients with hypertension that was inadequately controlled by the combination of a beta-adrenoceptor antagonist and a diuretic, nifedipine was shown to be effective in causing a further fall in arterial pressure; this finding was confirmed in a subsequent double-blind, placebo controlled study.

Forearm↗
PubMed1982

Response of forearm resistance vessels to verapamil and sodium nitroprusside in normotensive and hypertensive men: evidence for a functional abnormality of vascular smooth muscle in primary hypertension.

1. The response of the forearm resistance vessels to local intra-arterial infusion of verapamil and sodium nitroprusside has been assessed by a plethysmographic method in 23 men with normal arterial pressure and 35 men with primary hypertension. 2. In the 20 patients with hypertension for whom full dose-response curves were determined, the dilator response to verapamil was significantly greater than that in the normal controls, whereas the response to sodium nitroprusside was reduced. 3. Comparison of responses to the two dilators in individual subjects enabled the scattering effect of variables common to both drugs to be reduced. Analysis of the results in this way showed a highly significant difference between the hypertensive men as a whole and the normotensive controls (P less than 0.00001); 24 out of the 35 hypertensive men showed responses that were outside the normal range. 4. The abnormal pattern of response observed in the hypertensive group cannot be accounted for by structural changes in the vessels and strongly suggests a functional abnormality of the vascular smooth muscle.

Adult↗
PubMed1982

Nifedipine in the treatment of hypertension: report of a double-blind controlled trial.

1 The effect of oral nifedipine has been examined in patients with hypertension in whom arterial pressure was not adequately controlled by the combination of a beta-adrenoceptor antagonist (or alpha-methyldopa) and a diuretic. 2 In 42 patients, nifedipine (10 mg capsules) was added to the existing therapy in a final dose of 20-60 mg daily. Six patients had to stop the drug on account of side-effects. In the 36 patients who continued treatment, arterial pressure fell by an average of 24/9 mmHg supine and 26/10 mmHg standing. 3 In 11 of these patients who subsequently completed a double-blind, cross-over, placebo controlled trial, nifedipine (30-60 mg daily) was found to reduce arterial pressure by an average of 19/11 mmHg supine and 21/12 mmHg standing. 4 In all 11 patients who were changed to a sustained release preparation of nifedipine, control of arterial pressure was at least as good as it had been when taking the capsules.

Adult↗
PubMed1981

A method for assessing responses of small arteries in man: effect of physiological and pharmacological stimuli.

1. A method has been developed for estimating resistance to blood flow in the collateral arteries around the elbow. Arterial pressure is recorded continuously from the radial artery and blood flow in the forearm and hand is measured by venous occlusion plethysmography. The brachial artery is occluded for short periods, and the pressure drop across the collaterals and the flow through them are determined. From these observations an index of resistance can be calculated. 2. During 2 min occlusions of the brachial artery, collateral arterial resistance fell progressively to reach a level that was on average 45% lower than the initial resistance (P less than 0.01). 3. There was an inverse relation between distending pressure in the collateral arteries and calculated resistance. 4. Ergotamine tartrate (0.25 mg intravenously) increased collateral resistance by an average of 135%. Glyceryl trinitrate (0.5 mg sublingually) reduced collateral resistance by an average of 45%. Hydrallazine and isoprenaline had an inconsistent dilator effect; the direct action of these drugs may have been offset by the reduction in distending pressure which they induced. 5. The elbow collateral arteries provide a useful model for studying physiological and pharmacological responses of small limb arteries in man.

Adult↗
PubMed1980

Acquired tolerance to dilator action of hydrallazine during oral administration.

1 The effect on forearm blood flow of local intra-arterial infusion of hydrallazine has been studied in twelve patients with essential hypertension and six normal subjects. 2 When the patients with hypertension were not taking hydrallazine by mouth, they responded to intra-arterial infusions with a dose-dependent increase in forearm blood flow that was not significantly different from that in normal subjects. 3 When the patients were taking hydrallazine by mouth, the increase in forearm flow in response to intra-arterial infusions was reduced and forearm vascular resistance did not fall as low as it did in the control study (P less than 0.01). 4 In four patients, the response to intra-arterial hydrallazine was attenuated to a major extent, and in three of these, there was little or no response to oral treatment. In eight patients, the response to intra-arterial hydrallazine did not fall below one half of that in the control study and this minor reduction in sensitivity might be expected to impair, but not abolish, the response to oral treatment. 5 It is concluded that the resistance vessels commonly develop tolerance to the dilator action of hydrallazine during long-term oral therapy. In some patients a high degree of tolerance develops and this is an important cause of failure to respond to oral treatment.

Administration, Oral↗