Editorial Commentary Central Blood Pressure Under Angiotensin and Calcium Channel Blockade

Hemodynamic studies have shown that, in healthy subjects, there is a gradual widening of the height of the pressure waveform as it travels from the central (aortic) elastic arteries to the peripheral muscular arteries (brachial artery)1 (Figure). This disparity, which tends to disappear in the presence of vascular disease/aging, does not require any additional energy input within the arterial system, because the mean arterial pressure (MAP) and even the diastolic blood pressure (BP) remain almost unchanged between the 2 arterial sites. This finding is mainly attributed to the gradual increase (ie, amplification) of systolic BP (SBP) or pulse pressure (PP) along the arterial tree and is conventionally quantified as the ratio of the SBP or PP between the 2 sites (eg, SBP arm:SBP aorta)1 (Figure). In the present issue of Hypertension, Matsui et al2 have shown the superiority of calcium channel blockers (CCBs) over diuretics using the following protocol: the angiotensin receptor blocker olmesartan was combined with the CCB azelnidipine and compared with the same olmesartan associated with the diuretic hydrochlorothiazide. Central SBP was reduced to a greater degree with the CCB than with the hydrochlorothiazide. This resulted in an increase of SBP and PP amplification with the CCB, despite the lack of a significant difference in the brachial SBP reduction between the 2 strategies. In the past, 2 studies3,4 have tested the effects of combined antihypertensive therapies on SBP and PP amplification using an angiotensin-converting enzyme inhibitor associated with a CCB or diuretic versus the -blocking agent atenolol (either alone or in combination). Before commenting on the beneficial action of CCB, we briefly summarize the pharmacological effect of an angiotensin receptor blocker and/or angiotensin-converting enzyme inhibitor on SBP and PP amplification and, finally, discuss the potential clinical implications of antihypertensive drug treatment focusing on central hemodynamics and on the cardiovascular (CV) outcomes obtained from large clinical trials. Central BP, SBP, and PP Amplification and Angiotensin II Blockade The BP curve consists of 2 components: a steady and nonamplifiable component, the MAP, that depends on cardiac output and peripheral arterial resistance (microcirculation) and a pulsatile and amplifiable component (ie, the PP), that depends on large artery stiffness and pressure wave reflection (macrocirculation). It is essential to notice this distinction, because the transduction mechanisms governing MAP and PP differ markedly, involving apparently either focal adhesion kinase for MAP or oxygen free radicals for PP.5 Angiotensin II (ANGII) blockade is mainly associated with a reduction of vascular resistance and MAP. In contrast, the effects on central and peripheral PPs have been poorly investigated despite their well-established interactions with oxygen free radicals. Studies on animal models and humans suggest that ANGII blockade is associated with reverse remodeling of both small and large arteries via specific mechanisms, including anti-inflammatory effects and mainly change of arterial attachments linking 5ß1-integrin to its specific ligand fibronectin.6,7 Such effects are important to obtain a significant and selective reduction of central PP and arterial stiffness under ANGII blockade.6 In hypertensive rats on a low-salt diet (but not a high-salt diet), ANGII blockade by valsartan normalizes central PP ( 50 mm Hg) but not MAP for the same drug dosage.7 In hypertensive subjects under ANGII blockade, carotid-brachial SBP and PP amplifications are increased. ANGII blockade improves or even normalizes the structure of small resistance arteries and, at the same time, reduces pressure wave reflections, suggesting a cause-and-effect relationship between the 2 factors.3,8 In the study by Matsui et al,2 ANGII inhibition by olmesartan may have greatly contributed to independently lower central PP and aortic stiffness. The same mechanisms are not observed under CCB blockade.6