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Biomedical subjects

L G Howes

Publications and source records attributed to L G Howes.

At least 91 records · Page 5Linked to original sources
PubMed1989

Blood pressure variability in tetraplegic patients with autonomic hyperreflexia.

Autonomic hyperreflexia (AH) is a syndrome characterised by profound pressor responses, sweating and headache which occurs in tetraplegic patients in response to a variety of stimuli below the level of cord injury. The pathogenesis of this syndrome is unclear but may be associated with increased blood pressure (BP) variability in these patients. To investigate this possibility, 24 hour ambulatory BP monitoring was performed utilising the Spacelabs 5300 Ambulatory BP system in 30 patients: 10 normal subjects, 10 spinal cord injury (SCI) patients who had never experienced AH and 10 SCI patients who had experienced recent episodes of AH (but with no symptoms during the study period). There were no statistically significant differences in systolic BP (SBP), diastolic BP (DBP) or heart rate (HR) between the three groups. The average of the coefficients of variation of SBP, DBP and HR within each subject over the study period were calculated. Tetraplegic patients who had recently experienced episodes of AH had greater SBP, DBP and HR variability than normal persons (p less than 0.01, p less than 0.005, p less than 0.005) and greater DBP and HR variability than SCI patients who had never experienced AH (p less than 0.01, p less than 0.05). AH may represent the symptoms associated with the upper extremes of this BP variability. The increased variability may be the result of enhanced cardiovascular responsiveness to noradrenaline and arginine vasopressin or because of the absence of descending inhibitory pathways in the decentralised cord that would normally suppress spinal sympathetic reflexes.

Adult↗
PubMed1989

Cardiac 3,4-dihydroxyphenylethylene glycol (DHPG) and catecholamine levels in a rat model of left ventricular failure.

Cardiac norepinephrine (NE), dopamine (DA), epinephrine (Epi), and dihydroxyphenylethylene glycol (DHPG) (a major neuronal metabolite of NE) content were measured in rats with cardiac failure resulting from left ventricular myocardial infarction (LVMI) induced by coronary ligation. The ratio of DHPG/NE was significantly higher in both the right ventricle and interventricular septum of rats with LVMI compared with controls, reflecting a tendency for cardiac DHPG content to rise and NE content to fall during cardiac failure. Cardiac DA and Epi content did not significantly differ between rats with LVMI and controls. Elevated DHPG/NE ratios apparently reflected the increase in NE turnover that accompanies elevated sympathetic activity in heart failure more precisely than changes in NE levels or DHPG levels alone. Furthermore, DHPG/NE ratios are not influenced by increases in cardiac weight due to cardiac hypertrophy. The DHPG/NE ratios may be a useful index of cardiac sympathetic activity for future studies of the effects of drug treatment of cardiac failure in this animal model.

Animals↗
PubMed1989

Effects of sodium restriction on cardiac 3,4-dihydroxyphenylethylene glycol and catecholamine levels in rats.

1. The effects of low or high sodium intake for 4 weeks on cardiac catecholamines and 3,4-dihydroxyphenylethylene glycol (DHPG) levels were studied in adult female Wistar rats. 2. Rats receiving the low sodium diet had significantly higher plasma renin activity than rats receiving the high sodium diet. 3. Dopamine concentrations in both the right and left ventricle were significantly higher in the low salt compared with the high salt rats, but noradrenaline, adrenaline and DHPG levels did not differ significantly between the two groups. 4. These data do not support previous reports that sodium restriction reduces cardiac noradrenaline release, but suggest that alterations in sodium intake may influence cardiac noradrenaline metabolism.

Animals↗
PubMed1989

Cardiac 3,4-dihydroxyphenylethylene glycol (DHPG) and catecholamine levels during perindopril therapy of chronic left ventricular failure in rats.

1. Left ventricular myocardial infarction was induced in female Wistar rats by ligation of the left anterior descending coronary artery. 2. One month following operation, rats with infarcts developed marked cardiomegaly compared to sham operated rats, indicating the presence of chronic left ventricular failure. 3. The ratio of the noradrenaline metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) to noradrenaline (NA) was elevated in the right ventricle of rats with heart failure one month following infarction, suggesting a chronic increase in cardiac sympathetic activity. 4. Perindopril therapy for one month commenced 4 weeks after infarction returned cardiac weights to normal and significantly reduced right ventricular DHPG/NA ratios. 5. The results suggest that ACE inhibition with perindopril reduces elevated levels of cardiac sympathetic activity in rats with chronic left ventricular failure and leads to regression of cardiomegaly.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Rise in plasma noradrenaline with age results from an increase in spillover rate.

Venous plasma noradrenaline (NA) kinetics, determined using steady-state intravenous infusions of subpressor doses of [3H] NA, were measured in 8 young, 13 middle-aged and 8 elderly subjects. Plasma NA concentrations were 0.71 nmol/l (0.25-0.98) in the young, 1.90 nmol/l (0.98-3.65) in the middle-aged and 3.03 nmol/l (1.15-3.85) in the elderly (young vs. elderly, p less than 0.001). NA spillover rates were 2.07 nmol/l/m2 (1.05-4.91) in the young, 3.91 nmol/l/m2 (1.62-9.44) in the middle-aged and 7.57 nmol/l/m2 (4.38-24.0) in the elderly (young vs. elderly, p less than 0.001). Plasma NA clearance was similar in young and elderly subjects. NA spillover was positively correlated with age (r = 0.58; p less than 0.01) and was not independently related to blood pressure. The rise in plasma NA with age results from an increase in spillover rate rather than any alteration in clearance.

Adult↗
PubMed1989

Single-dose and steady-state pharmacokinetics of doxazosin given in combination with chlorothiazide to hypertensive subjects.

The pharmacokinetics of doxazosin were determined in hypertensive subjects after a single dose of 1 mg, and at steady-state while receiving doses of 1, 2, 4 and 8 mg of the drug daily. Chlorothiazide 500 mg once daily was administered as additional therapy throughout the study. After a single dose doxazosin was rapidly absorbed, with peak plasma drug concentrations (Cmax) occurring after 2.1 +/- 0.4 hours. The elimination half-life in plasma was 10.7 +/- 1.2 hours. These parameters remained essentially unchanged during maintenance administration of doxazosin at each of the dose levels. Calculations of Cmax and area under the concentration-time curve (AUC0----infinity) indicated that the pharmacokinetic disposition of the drug remained linear over the dose range 1 to 8 mg.

Adult↗
PubMed1989

Alpha blockers and vasodilating beta blockers--influence on factors involved in the pathogenesis of vascular disease in patients with hypertension.

Antihypertensive drugs that interact with adrenoceptors have certain advantages and disadvantages (on the treatment of hypertension). Alpha-1 antagonists such as prazosin have favorable effects on plasma lipids but may produce excessive postural falls in blood pressure, particularly following the initial dose. Recently developed alpha-1 antagonists (doxazosin, terazosin) have longer durations of action than prazosin, allowing less frequent administration. Beta blockers may be cardioprotective but in contrast to alpha-1 antagonists tend to have adverse effects on plasma lipids. Drugs with combined beta and alpha-1 blocking activity such as labetalol have favorable metabolic effects but postural hypotension remains a problem. Recently developed drugs with different alpha-1/beta blocking ratios that differ from labetalol may prove to be more popular clinically. Several beta blockers with vasodilator activity which is not due to alpha-1 blockade have also been developed. These drugs appear to have favorable metabolic effects similar to drugs with alpha-1 blocking activity, but do not cause postural hypotension.

Adrenergic alpha-Antagonists↗
PubMed1988

Effects of antihypertensive drugs on cardiovascular risk factors.

1. Large scale studies have failed to show a substantial benefit of antihypertensive therapy on the incidence of ischaemic heart disease. 2. This may be due to adverse effects of antihypertensive drugs on plasma lipoproteins or because of failure to adequately manage other risk factors for atherogenesis. 3. Hypercholesterolaemia is very common in patients receiving antihypertensive therapy, and is difficult to manage successfully using existing treatment strategies. 4. The achievement of a reduction in mortality and morbidity from ischaemic heart disease amongst hypertensive patients represents a major challenge. Success will probably depend upon the development of adequate methods of lowering plasma cholesterol levels.

Antihypertensive Agents↗
PubMed1988

Neurohumoral responses to chronic myocardial infarction in rats.

In chronic cardiac failure, various neurohumoral mechanisms are activated to sustain blood volume, blood pressure, and organ perfusion. Using the coronary artery ligation model of heart failure in the rat, we have measured changes in vasoactive hormone secretion and related these changes to salt and water status during a 1-month period. When compared with controls, rats with infarction had a marked rise in plasma atrial natriuretic peptide (294 +/- 59 vs. 79 +/- 10 pg/ml, p less than 0.001) although there was no increase in total exchangeable body sodium. Plasma renin activity and plasma aldosterone concentrations were the same for both rats with infarction and controls. Similarly, there were no significant differences in plasma arginine vasopressin, plasma osmolality, or plasma sodium concentration in rats with infarction. Ventricular norepinephrine levels were reduced in animals with infarction (p less than 0.01). Plasma atrial natriuretic peptide levels were raised in this model of chronic left ventricular failure. However, there was no salt retention and little stimulation of the renin-angiotensin-aldosterone system or vasopressin. The results suggest that high circulating atrial natriuretic peptide levels may prevent or limit salt and water retention, either directly or indirectly, by inhibiting the renin-angiotensin-aldosterone system.

Aldosterone↗
PubMed1987

Clopamide: plasma concentrations and diuretic effect in humans.

Clopamide pharmacokinetics were determined after oral doses of 5, 10, and 20 mg in normal volunteers. Maximum plasma concentrations occurred within 2 hours and were followed by a monoexponential decline with an elimination half-life of approximately 10 hours. There was an approximately linear relationship between dose and the AUC. Urinary sodium, chloride, and potassium excretion rates indicated that the peak diuretic activity corresponded with peak plasma drug concentrations and probably continued for 12 to 24 hours. There was little difference between the total sodium and chloride output after each dose of clopamide, suggesting that 5 mg may have been close to the top of the dose-response curve. Chlorothiazide, 500 mg, caused less sodium and chloride output with similar potassium loss. During chronic administration to patients with hypertension, hypokalemia was more marked with clopamide, 10 mg daily, than with clopamide, 5 mg, or chlorothiazide, 500 mg daily.

Administration, Oral↗
PubMed1987

Neurotransmitters and neuropeptides in blood pressure regulation in the spontaneously hypertensive rat.

Studies of the roles played by neurotransmitters in the development of hypertension in the spontaneously hypertensive (SHR) rat are complicated by the presence of genetic differences between SHR and normotensive control rats, which are not related to differences in blood pressure. One approach that may be used in an attempt to overcome this difficulty is to study the manner in which neurotransmitter and metabolite levels change with age, and to relate these changes to alterations in blood pressure with ageing. Noradrenaline (NA) levels in the brainstem and spinal cord of SHR and Wistar Kyoto rats fell with age, while 3,4-dihydroxyphenylethyleneglycol (DHPG) levels (a neuronal metabolite of noradrenaline) remained constant. Similar changes were seen when NA and DHPG levels were measured in the discrete brainstem A1, A2, and C2 region, and when adrenaline, NA, and DHPG levels were examined in the C1 region. Differences in age-related changes of neuropeptide Y (NPY) levels were also found in the ventromedial nucleus of the hypothalamus and the locus coeruleus, and of beta-endorphin in the anterior hypothalamic nucleus, the paragigantocellular nucleus of the brainstem, and the locus coeruleus. These changes may indicate either a progressive increase in the activity of neurons in the sympathoexcitatory C1 region or a progressive reduction in the activity of vasodepressor A1, A2, and C2 regions with ageing, or both. However, changes in catecholamines and metabolites with age were similar in both strains and therefore cannot readily explain the more rapid rise in blood pressure with ageing in SHR rats.

Aging↗
PubMed1987

Comparison of pharmacokinetics and pharmacodynamics of adrenoceptor agonists and antagonists as antihypertensive agents.

Central and peripheral alpha-adrenoceptors play an important role in cardiovascular regulation, and selective alpha 1-adrenoceptor antagonists and alpha 2-adrenoceptor agonists have an established place in the therapy of hypertension. Prazosin is a selective alpha 1-antagonist that is both effective in lowering blood pressure and well tolerated. However, the more recently developed alpha 1-antagonists doxazosin and terazosin offer the advantage of having longer half-lives, allowing once daily administration. Clonidine is a centrally acting alpha 2-agonist whose clinical use has often been limited by the dose dependent side effects of dry mouth and sedation, and the belief that it should be given three times per day. However, recent studies have shown that it has substantial antihypertensive efficacy with minimal side effects at low doses, and that half-life is long enough to allow twice daily administration. An improved understanding of the pharmacodynamics and pharmacokinetics of drugs acting on alpha-adrenoceptors allows a more rational approach to their clinical application.

Adrenergic alpha-Agonists↗