Lau Siu Wai Maggie. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 236-245). / List of Figures --- p.i / List of Tables --- p.viii / List of Abbreviations --- p.x / Abstract --- p.xii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Postulated Pathophysiology of Essential Hypertension --- p.1 / Chapter 1.2 --- Measurement of Cardiac Output (CO) by Transthoracic Electrical Bioimpedance (TEB) and Other Methodologies --- p.6 / Chapter 1.3 --- Measurement of Blood Pressure --- p.10 / Chapter 1.4 --- Use of Antihypertensive Agents in Essential Hypertension --- p.12 / Chapter Chapter 2. --- The Method of Transthoracic Electrical Bioimpedance --- p.15 / Chapter 2.1 --- Introduction --- p.15 / Chapter 2.2 --- Development of Theory --- p.18 / Chapter 2.3 --- Measurements of Haemodynamic Parameters --- p.24 / Chapter 2.4 --- Literature Review - Validity of the Technique --- p.30 / Chapter Chapter 3 --- A Study on Reproducibility of Thoracic Electrical Bioimpedance in Healthy Subjects --- p.39 / Chapter 3.1 --- Objectives --- p.39 / Chapter 3.2 --- Methodology --- p.39 / Chapter 3.2.1 --- Subjects --- p.39 / Chapter 3.2.2 --- Study design --- p.41 / Chapter 3.2.3 --- Non-invasive haemodynamic monitoring --- p.41 / Chapter 3.2.4 --- Blood Pressure Measurement --- p.43 / Chapter 3.2.5 --- Isometric Exercise --- p.43 / Chapter 3.2.6 --- Data analysis --- p.44 / Chapter 3.2.7 --- Statistical analysis --- p.46 / Chapter 3.3 --- Results --- p.50 / Chapter 3.3.1 --- Systolic blood pressure --- p.50 / Chapter 3.3.2 --- Diastolic blood pressure --- p.52 / Chapter 3.3.3 --- Mean arterial pressure --- p.54 / Chapter 3.3.4 --- Heart rate --- p.55 / Chapter 3.3.5 --- Thoracic fluid index --- p.58 / Chapter 3.3.6 --- Stroke index --- p.60 / Chapter 3.3.7 --- Cardiac index --- p.62 / Chapter 3.3.8 --- Systemic vascular resistance index --- p.65 / Chapter 3.4 --- Discussion --- p.70 / Chapter Chapter 4 --- Literature Review --- p.73 / Chapter 4.1 --- Atenolol: Beta-adrenoceptor antagonists with β1-selectivity --- p.73 / Chapter 4.2 --- Pindolol: Beta-adrenoceptor antagonists with ISA --- p.78 / Chapter 4.3 --- Alpha1-adrenoceptor antagonists --- p.81 / Chapter 4.4 --- Angiotensin Converting Enzyme Inhibitors --- p.84 / Chapter 4.5 --- Calcium Channel Blockers --- p.87 / Chapter 4.6 --- Central Alpha Agonist --- p.91 / Chapter 4.7 --- Thiazide Diuretics --- p.94 / Chapter Chapter 5 --- The Integrated Hypertension Study --- p.97 / Chapter 5.1 --- Objectives --- p.97 / Chapter 5.2 --- Methodology --- p.97 / Chapter 5.2.1 --- Subjects --- p.97 / Chapter 5.2.2 --- Study design --- p.109 / Chapter 5.2.3 --- Non-invasive haemodynamic monitoring --- p.110 / Chapter 5.2 4 --- Blood Pressure Measurement --- p.111 / Chapter 5.2.5 --- Isometric Exercise --- p.111 / Chapter 5.2.6 --- Data analysis --- p.111 / Chapter 5.2.7 --- Statistical analysis --- p.112 / Chapter 5.2.8 --- Limitations of the study --- p.113 / Chapter 5.3 --- Results --- p.117 / Chapter 5.3.1 --- Atenolol --- p.117 / Chapter 5.3.2 --- Pindolol --- p.125 / Chapter 5.3.3 --- Doxazosin --- p.132 / Chapter 5.3.4 --- Enalapril --- p.138 / Chapter 5.3.5 --- Nifedipine Retard --- p.145 / Chapter 5.3.6 --- Methyldopa --- p.152 / Chapter 5.3.7 --- Cyclopenthiazide --- p.160 / Chapter 5.4 --- Comparisons of the anti-hypertensive drugs studied --- p.167 / Chapter 5.4.1 --- Baseline values --- p.167 / Chapter 5.4.2 --- Percentage changes after active treatment --- p.170 / Chapter 5.5 --- Discussion --- p.196 / Chapter 5.5.1 --- Atenolol --- p.196 / Chapter 5.5.2 --- Pindolol --- p.199 / Chapter 5.5.3 --- Doxazosin --- p.200 / Chapter 5.5.4 --- Enalapril --- p.202 / Chapter 5.5.5 --- Nifedipine Retard --- p.203 / Chapter 5.5.6 --- Methyldopa --- p.204 / Chapter 5.5.7 --- Cyclopenthiazide --- p.205 / Chapter 5.5.8 --- Comparison of the anti-hypertensive drugs studied --- p.206 / Chapter Chapter 6 --- Acute haemodynamic effects of Atenolol and Pindolol --- p.208 / Chapter 6.1 --- Objectives --- p.208 / Chapter 6.2 --- Methodology --- p.208 / Chapter 6.2.1 --- Subjects --- p.208 / Chapter 6.2.2 --- Study Design --- p.209 / Chapter 6.2.3 --- Statistical analysis --- p.209 / Chapter 6.3 --- Results --- p.211 / Chapter 6.3.1 --- Acute haemodynamic changes of atenolol --- p.211 / Chapter 6.3.2 --- Acute and short-term haemodynamic changes of atenolol --- p.219 / Chapter 6.3.3 --- Acute haemodymmic changes of pindolol --- p.221 / Chapter 6.3.4 --- Acute and short-term haemodymmic changes of pindolol --- p.222 / Chapter 6.3.5 --- Comparison of the acute haemodymmic effects of atenolol and pindolol --- p.226 / Chapter 6.4 --- Discussion --- p.230 / Chapter Chapter 7 --- Conclusion --- p.232 / References --- p.236 / Acknowledgements

The current recommendations by the American Heart Association for health promotion are that all persons should partake in regular physical activity in order to reduce the risk of cardiovascular disease. Regular physical exercise reduces blood pressure and is an important component of the management of hypertension. It is therefore important that patients with hypertension participate in habitual physical exercise. Many hypertensive patients who exercise will require anti-hypertensive medication. However, some antihypertensive agents cause fatigue during exercise. In order for patients to gain the full benefits of an active lifestyle, it is important that the prescribed antihypertensive agent does not prevent them performing and enjoying sustained exercise. It has been well documented that β-blockers cause premature fatigue during physical exercise. The effects on exercise performance of other first line antihypertensive medications, such as calcium channel antagonists have not been extensively investigated. In particular, the effects of these agents on prolonged submaximal exercise endurance have not been well studied. The object of this thesis was to compare the effects of isradipine, a dihydropyridine calcium channel antagonist, to those of atenolol, a β₁-selective antagonist, on maximal and submaximal exercise performance and on short duration high-intensity exercise in physically active hypertensive patients. The study design was a crossover trial where drug treatments were double blinded and randomised. Physically active volunteers with mild to moderate hypertension were recruited. 11 subjects performed i) progressive exercise to exhaustion for determination of maximal oxygen consumption (VO₂max), maximal work load and cardiorespiratory responses to maximal exercise, ii) prolonged submaximal exercise for determination of exercise endurance, cardiorespiratory responses and ratings of perceived exertion (APE), and iii) short duration, high intensity exercise consisting of a 30 second maximal exercise test (Wingate test) to determine skeletal muscle power output, following 4 weeks ingestion of isradipine (2.5mg bd), atenolol (50mg bd) or placebo. Diastolic blood pressure at rest was reduced by both atenolol and isradipine, but was lowered to a greater extent by atenolol (83.3 vs 89.0 vs 96.1 mmHg, atenolol vs isradipine vs placebo, p<.0005). Systolic blood pressure at rest tended to be similarly reduced by both agents, but was significantly reduced during maximal and submaximal exercise by atenolol only (p<.001, atenolol vs isradipine, placebo). Heart rate at rest and during maximal and submaximal exercise was decreased by atenolol only (p<.0005, atenolol vs isradipine, placebo). Maximal exercise performance was reduced after atenolol ingestion compared to placebo but not after isradipine ingestion. Peak workload achieved during the maximal exercise test was decreased after atenolol but unchanged after isradipine ingestion (214 vs 243 W, atenolol vs placebo, p<.01). Similarly, VO₂max was reduced after atenolol compared to placebo but was unchanged after isradipine ingestion (33.6 vs 36.4, 33.6 vs 36.1 mlO₂/kg/min, atenolol vs placebo, atenolol vs isradipine, p<.05). Both atenolol and isradipine ingestion reduced submaximal endurance time compared to placebo (27.8 vs 46.4, 34.4 vs 46.4 min, atenolol vs placebo, isradipine vs placebo, p<.005), and increased rating of perceived exertion (APE) after 30 min of submaximal exercise (p<.05). Submaximal oxygen consumption (VO₂), ventilation, respiratory exchange ratio (REA) and blood lactate, glucose and free fatty acid concentrations were not altered after the ingestion of either agent. Neither agent influenced peak skeletal muscle power, total work done, or rate of fatigue during the Wingate test compared to placebo. The results of these studies indicate that impaired performance and increased RPE during submaximal exercise after ingestion of either atenolol or isradipine is not due to alterations of ventilation, VO₂, RER, or blood lactate, glucose and free fatty acid concentrations during prolonged submaximal exercise. Similarly, reduced submaximal exercise performance after atenolol or isradipine ingestion is not due to factors which would also limit the ability of skeletal muscle to perform short duration, high intensity exercise before a bout of prolonged exercise. This study demonstrates that prolonged submaximal exercise testing can reveal an impairment in exercise performance after ingestion of antihypertensive medication which is not evident during maximal exercise testing. This finding is important as prolonged submaximal exercise is the form of exercise which most hypertensive patients actually perform. Further research is required on the effects of anti-hypertensive medications on submaximal exercise performance before firm recommendations can be made regarding medications most suitable for the physically active hypertensive patient. The results of these and other studies indicate that it is not yet possible to make claims that the calcium channel antagonist agents are without effect on physical exercise performance in physically active hypertensive patients.