T he relationship between sodium and blood pressure (BP) continues to be the focus of intense research. In humans, the impact of sodium on systolic BP (SBP), diastolic BP (DBP), mean BP, and pulse pressure (PP) is currently thought to be quite similar for the 4 pressures and to occur practically with identical consequences (see reviews [1][2][3][4][5][6][7][8] ). In this review, the effect of sodium on SBP is taken into consideration mainly for a very simple but important reason: in recent years, SBP and PP have become the parameters the most difficult to control in hypertensive subjects, which is the principal goal of most antihypertensive drugs. 1 Central (aortic) SBP is a complex parameter that is influenced both by cardiac (stroke volume and ventricular ejection) and vascular (arterial and venous stiffness and wave reflections) factors. 1 Stroke volume, the ratio between cardiac output and heart rate, depends not only on cardiac structure and function but also on venous return. Through the extracellular and intravascular spaces and their elastic properties, stroke volume and, hence, SBP are strongly associated with sodium balance, ie, with the relationship between sodium intake and its urinary elimination, and, finally, the traditional pressure-diuresis mechanism. 4 This pathway, which mainly affects the venous circulation, requires a low and steady BP, together with a vast storage capacity for salt and water. Another important pathway affects the high-pressure pulsatile arterial system, in which the SBP level is achieved through increased arterial stiffness and disturbed wave reflections. These hemodynamic parameters are strongly influenced by sodium intake, and their anomalies are mostly seen in subjects Ͼ50 years old. 1,2,5,7,9 Note that, in humans, the volume and elasticity of the arterial space are very low compared with the corresponding values for the venous system. 1 We have 2 principal aims for this review. First, how does dietary sodium influence vascular stiffness and, through mechanisms affecting the venous circulation, modulate stroke volume and SBP, potentially leading to hypertension? Second, how does sodium intake adversely affect the arterial circulation and, through increased arterial stiffness and wave reflections, potentially worsen hypertension and exacerbate cardiovascular risk? These 2 questions are detailed successively after a brief historical review of the traditional relationships between sodium and BP and a summary of their interactions with the renin-angiotensin-aldosterone system (RAAS). Other hormonal factors, with the exception of antidiuretic hormone, are beyond the scope of this review. Sodium, SBP, and Cardiovascular Risk: A Brief Historical OverviewOver the last few decades, a considerable body of evidence has shown major links along with cause-and-effect relationships between salt intake and BP. They have given rise to numerous publications and reviews, summarized here. [1][2][3][4][5][6][7][8] In most studies, SBP and DBP were considered to be equivalent mechanical facto...

We examined the arterial phenotype of mice lacking alpha(1)-integrin (alpha(1)(-/-)) at baseline and after 4 wk of ANG II or norepinephrine (NE) administration. Arterial mechanical properties were determined in the carotid artery (CA). Integrin expression, MAPK kinases, and focal adhesion kinase (FAK) were assessed in the aorta. No change in arterial pressure was observed in alpha(1)(-/-) mice. Elastic modulus-wall stress curves were similar in alpha(1)(-/-) and alpha(1)(+/+) animals, indicating no change in arterial stiffness. The rupture pressure was lower in alpha(1)(-/-) mice, demonstrating decreased mechanical strength. Lack of alpha(1)-integrin was accompanied by an increase in beta(1)-, alpha(v)-, and alpha(5)-integrins but no change in alpha(2)-integrin. ANG II increased medial cross-sectional area of the CA in alpha(1)(+/+), but not alpha(1)(-/-), mice, whereas equivalent pressor doses of NE did not produce a significant increase in either group. In alpha(1)(+/+) mice, ANG II induced alpha(1)-integrin expression and smooth muscle cell (SMC) hypertrophy in the CA in association with increased aortic expression of alpha-smooth muscle actin and smooth muscle myosin heavy chain and phosphorylation of ERK1/2, p38 MAPK, and FAK. ANG II did not induce SMC hypertrophy or phosphorylation of p38 MAPK and FAK in alpha(1)(-/-) mice. A functional anti-alpha(1)-integrin antibody inhibited in vitro the ANG II-induced phosphorylation of FAK and p38 MAPK. In conclusion, alpha(1)(-/-) mice exhibit a reduced mechanical strength at baseline and a lack of ANG II-induced SMC hypertrophy. These results emphasize the importance of alpha(1)beta(1)-integrin in p38 MAPK and FAK phosphorylation during vascular hypertrophy in response to ANG II.

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