Selective Reduction of Central Pulse Pressure Under Angiotensin Blockage in SHR: Role of the Fibronectin–α5β1 Integrin Complex

Antihypertensive drug treatment significantly reduces cardio­ vascular (CV) morbidity and mortality in hypertensive subjects. Based on meta­analyses, it has been proposed that stroke prevention could be better achieved using calcium­ entry blockers (CEB) whereas coronary disease prevention could be better improved under angiotensin­converting enzyme inhibitors (ACEIs).1 However, for most authors, lowering the CV risk exclusively reflects the degree of blood pressure (BP) reduction obtained by drug(s) regardless of the medica­ tion used.1,2 In therapeutic trials, diastolic BP (DBP) is easily normalized by medication (<90 mm Hg) whereas systolic BP (SBP) is not (>140 mm Hg).3 Thus it is important to determine which class of antihypertensive agent might achieve a more selective SBP decrease in hypertensive subjects. Results from the REASON and the CAFE controlled trials4,5 have shown that, at a given ventricular ejection, SBP and pulse pressure (PP) could be predominantly reduced through decreases of arterial stiffness, and/or wave reflections. Such results had two particularities. First, calcium­channel block­ ade by amlodipine and/or angiotensin blockade by the ACEI perindopril were used to lower SBP and PP and both were compared to the same β­blocking agent, atenolol. Second, diminished cardiac hypertrophy (for REASON) and reduction of CV outcomes (for CAFE study) were observed under ACEI and/or CEB, and were consistently more pronounced using central rather than brachial BP measurements, when com­ pared to atenolol. Taken together, these findings highlighted the major importance of investigating central BP, aortic stiff­ ness and wave reflections under chronic ACEI and/or CEB administration to obtain selective SBP and PP reductions.4,5 Arterial stiffness and wave reflections have been thoroughly investigated under treatment with ACEI and angiotensin­II type­1 receptor antagonists.6–8 In contrast, little has been done 1INSERM, Nancy, France; 2Henri Poincare University, Nancy, France; 3Department of Pharmacie, Groupe Hospitalier Paris Saint–joseph, Paris, France; 4Université Pierre et Marie Curie, Paris, France; 5Université Paris Descartes, Paris, France; 6Assistance Publique-Hôpitaux de Paris, Paris, France; 7Hôtel-Dieu, Centre de Diagnostic et de Thérapeutique, Paris, France. Correspondence: Michel E. Safar ([email protected])