Mercier Nathalie, Labat Carlos, Louis Huguette, Cattan Valerie, Benetos Athanase, Safar Michel E, Lacolley Patrick
INSERM, U684, Nancy, France; Université Henri Poincaré, UFR Médecine, Nancy, France.
Am J Hypertens. 2007 Mar;20(3):319-25. doi: 10.1016/j.amjhyper.2006.09.002.
We examined the effects of early high salt diet (HSD) and angiotensin II type 1 (AT1) receptor antagonist valsartan (Val) on mortality and carotid distensibility in surviving spontaneously hypertensive rats (SHRs).
The HSD was initiated either early (week 4 after birth) or late (week 10), continued until 20 weeks of age, and compared to normal salt diet (NSD) groups. Valsartan was given from the fourth week after birth.
Eighty-six percent of the rats died in early HSD on placebo, 70% in early HSD on Val-3 mg, 35% in early HSD on Val-30 mg, and 13% in late HSD on placebo. Mean arterial pressure (MAP) was higher in the early HSD and late HSD groups on placebo compared with NSD. The Val-30 mg reduced MAP in all except early HSD groups. Distensibility at MAP (operational distensibility) was lower in late HSD on placebo than in NSD placebo groups. The Val-30 mg increased distensibility in NSD groups. There was no effect of Val in late HSD and early HSD groups. Operational distensibility was negatively correlated with MAP and salt and positively correlated with Val treatment. All animals receiving HSD showed a higher isobaric distensibility in early HSD than in late HSD groups and a smaller distensibility in rats treated with Val.
Our results showed that administration of early HSD in SHR was associated together with a high mortality, a protective action of Val that increased longevity, and an increased level of isobaric distensibility. Survival in HSD groups suggest a direct role of angiotensin II in salt-induced cardiovascular mortality. This role is associated with MAP independent of changes in carotid stiffness.
我们研究了早期高盐饮食（HSD）和血管紧张素II 1型（AT1）受体拮抗剂缬沙坦（Val）对存活的自发性高血压大鼠（SHR）死亡率和颈动脉扩张性的影响。
早期（出生后第4周）或晚期（第10周）开始高盐饮食，持续至20周龄，并与正常盐饮食（NSD）组进行比较。从出生后第4周开始给予缬沙坦。
早期高盐饮食且服用安慰剂的大鼠中有86%死亡，早期高盐饮食且服用3mg Val的大鼠中有70%死亡，早期高盐饮食且服用30mg Val的大鼠中有35%死亡，晚期高盐饮食且服用安慰剂的大鼠中有13%死亡。与正常盐饮食组相比，早期高盐饮食和晚期高盐饮食且服用安慰剂组的平均动脉压（MAP）更高。除早期高盐饮食组外，30mg Val降低了所有组的MAP。晚期高盐饮食且服用安慰剂组在MAP时的扩张性（操作扩张性）低于正常盐饮食且服用安慰剂组。30mg Val增加了正常盐饮食组的扩张性。缬沙坦对晚期高盐饮食组和早期高盐饮食组没有影响。操作扩张性与MAP和盐呈负相关，与缬沙坦治疗呈正相关。所有接受高盐饮食的动物在早期高盐饮食组中的等压扩张性高于晚期高盐饮食组，且在接受缬沙坦治疗的大鼠中扩张性较小。
我们的结果表明，在自发性高血压大鼠中给予早期高盐饮食与高死亡率、缬沙坦增加寿命的保护作用以及等压扩张性水平升高有关。高盐饮食组的存活表明血管紧张素II在盐诱导的心血管死亡中起直接作用。这一作用与MAP相关，与颈动脉僵硬度的变化无关。
