Many individuals exhibit salt-sensitive forms of hypertension, in which elevated dietary salt intake leads to an increase in arterial blood pressure. This elevation of blood pressure is accompanied by an increase in peripheral vascular resistance. A particularly valuable genetic animal model of salt-sensitive hypertension is the Dahl salt-sensitive (Dahl S) rat, an inbred strain of rats in which elevation of dietary salt intake leads to an elevated vascular resistance and a substantial degree of hypertension. In Dahl S rats, the development of hypertension in response to elevated dietary salt intake is accompanied by a uniform increase in hemo-dynamic resistance throughout most of the peripheral vas-culature. In the spinotrapezius muscle, this increase in resistance is largely due to an intense constriction of proximal arterioles. The mechanisms responsible for this increased arteriolar tone include increased responsiveness to oxygen and a loss of tonic nitric oxide (NO) availability caused by reduced endothelial NO production and/or accelerated degradation of NO by reactive oxygen species.
In recent years, it has become increasingly clear that elevated dietary salt intake alone can lead to profound changes in the structure and function of resistance vessels of nor-motensive animals, as well as vessels of salt-sensitive experimental models of hypertension such as the Dahl S rat. These changes include microvascular rarefaction and an impaired relaxation of blood vessels in response to vasodilator stimuli such as hypoxia, acetylcholine, and prostacyclin. In normotensive Dahl salt-resistant (Dahl R) rats, elevated dietary salt intake also leads to an impaired dilation during the elevated shear stress that occurs in response to increased flow in the arteriole. The impaired dilation in response to increased flow in arterioles of Dahl R rats on high-salt diet appears to be due to a salt-induced suppression of NO activity in the absence of hypertension. Emerging evidence suggests that impaired vascular relaxation in normoten-sive animals on a high-salt diet involves alterations in the function of both the endothelium and the vascular smooth muscle cells, and that increased levels of oxidative stress in the vasculature can contribute to the impaired vascular relaxation in animals on high-salt diet.
The impaired relaxation of blood vessels of normoten-sive animals on high-salt diet in response to vasodilator stimuli such as hypoxia, acetylcholine, and prostacyclin appears to be due to the suppression of angiotensin II (ANG II) levels that occurs in response to high-salt diet, because continuous i.v. infusion of a low dose of ANG II to prevent salt-induced ANG II suppression restores normal vasodilator responses without raising blood pressure in normoten-sive animals on a high-salt diet. The direct effect of high-salt diet itself in contributing to microvessel rarefaction and impaired vascular relaxation in normotensive rats suggests that elevated dietary salt intake may be an important initial contributor to the increased vascular resistance in saltsensitive forms of hypertension, since it would tend to elevate vascular resistance even before the increase in arterial blood pressure. In combination with other predisposing factors for hypertension, such as impaired renal function, these changes not only could lead to the development of salt-sensitive hypertension, but also could play a major role in the maintenance and progression of the elevated vascular resistance in salt-sensitive forms of this disease.
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