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Successful treatment of hypertension is possible with limited side effects given the availability of multiple antihypertensive drug classes. This review describes the various ...pharmacological classes of antihypertensive drugs, under two major aspects: their mechanisms of action and side effects. The mechanism of action is analysed through a pharmacological approach, i.e. the molecular receptor targets, the various sites along the arterial system, and the extra-arterial sites of action, in order to better understand in which type of hypertension a given pharmacological class of antihypertensive drug is most indicated. In addition, side effects are described and explained through their pharmacological mechanisms, in order to better understand their mechanism of occurrence and in which patients drugs are contra-indicated. This review does not address the effectiveness of monotherapies in large randomized clinical trials and combination therapies, since these are the matters of other articles of the present issue. Five major pharmacological classes of antihypertensive drugs are detailed here: beta-blockers, diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers. Four additional pharmacological classes are described in a shorter manner: renin inhibitors, alpha-adrenergic receptor blockers, centrally acting agents, and direct acting vasodilators.
Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent ...literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.
Whereas vascular aging has been identified as an emerging cardiovascular risk factor, definitions of 'normal' and 'early' vascular aging (EVA) and their precise relationship with cardiovascular risk ...are currently equivocal. The present review discusses the concept of vascular aging; that structural and functional changes occur in the large arteries with aging; and EVA; that such age-associated changes are accelerated in individuals at increased cardiovascular risk; and their metrics; indeed, in order to provide a definition of when EVA occurs in clinical practice, reference values of normal and accelerated vascular aging are needed. Due to the complex nature of age-associated changes in the large arteries described above, there are different parameters relating to vascular aging which can be measured. These broadly include aortic and carotid stiffening; aortic and carotid lumen dilation; endothelial dysfunction (usually measured via brachial flow-mediated dilatation); and carotid intima-media thickness.
The beta-blocker atenolol is less effective than angiotensin-receptor blockers and calcium-channel blockers for reducing central blood pressure (BP). The trial was designed to determine whether the ...advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine. A prospective, randomized, blinded endpoint (PROBE design) parallel group, multicenter trial including 393 patients with essential hypertension resistant to 4 weeks of 5 mg of amlodipine was set out. Central systolic BP, augmentation index (AIx; either rough or adjusted on heart rate), and carotid-to-femoral pulse wave velocity were measured with applanation tonometry (SphygmoCor) at inclusion and after 8 and 24 weeks of active treatment with an amlodipine-valsartan combination (5/80 mg and then 10/160 mg) or an amlodipine-atenolol combination (5/50 mg and then 10/100 mg). From baseline to week 24, central systolic BP decreased significantly more in the amlodipine-valsartan group (-13.70+/-1.15 mm Hg; P<0.0001) than in the amlodipine-atenolol group (-9.70+/-1.10 mm Hg; P<0.0001; difference: -4.00 mm Hg 95% CI: -7.10 to -0.90; P=0.013), despite similar changes in brachial systolic BP. The difference in rough AIx reduction was -6.5% (95% CI: -8.3 to -4.7; P<0.0001) in favor of amlodipine-valsartan. AIx adjusted on heart rate was significantly reduced in favor of amlodipine-valsartan (-2.8% 95% CI: -4.92 to -0.68; P<0.01). Heart rate decreased significantly more with amlodipine-atenolol (difference: -11 bpm 95% CI: -14 to -8 bpm; P<0.001). Pulse wave velocity decreased by 0.95 m/s in both groups with no significant difference. Differences in central systolic BP and rough AIx remained significant after adjustment to the changes in heart rate. The amlodipine-valsartan combination decreased central (systolic and pulse) pressure and AIx more than the amlodipine-atenolol combination.
Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and ...structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.
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