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The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and associated metabolic disturbances. Multiple quantitative trait loci associated with hemodynamic and metabolic parameters have been mapped in the SHR. Recently, it has become possible to identify some of the specific quantitative trait gene (QTG) variants that underlie quantitative trait loci linked to complex cardiovascular and metabolic traits in SHR related strains. Recombinant inbred strains derived from SHR and Brown Norway progenitors, together with SHR congenic and transgenic strains, have proven useful for establishing the identity of several QTGs in SHR models. It is anticipated that the combined use of linkage analyses and gene expression profiles, together with the recently available genome sequences of both the SHR and Brown Norway strains and new methods for manipulating the rat genome, will soon accelerate progress in identifying QTGs for complex traits in SHR-related strains.

Background: Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. Methods: In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. Results: In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. Conclusions: Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism. [ABSTRACT FROM AUTHOR]

High-salt diets are a major cause of hypertension and cardiovascular (CV) disease. Many governments are interested in using food salt reduction programs to reduce the risk for salt-induced increases in blood pressure and CV events. It is assumed that reducing the salt concentration of processed foods will substantially reduce mean salt intake in the general population. However, contrary to expectations, reducing the sodium density of nearly all foods consumed in England by 21% had little or no effect on salt intake in the general population. This may be due to the fact that in England, as in other countries including the U.S.A., mean salt intake is already close to the lower normal physiologic limit for mean salt intake of free-living populations. Thus, mechanism-based strategies for preventing salt-induced increases in blood pressure that do not solely depend on reducing salt intake merit attention. It is now recognized that the initiation of salt-induced increases in blood pressure often involves a combination of normal increases in sodium balance, blood volume and cardiac output together with abnormal vascular resistance responses to increased salt intake. Therefore, preventing either the normal increases in sodium balance and cardiac output, or the abnormal vascular resistance responses to salt, can prevent salt-induced increases in blood pressure. Suboptimal nutrient intake is a common cause of the hemodynamic disturbances mediating salt-induced hypertension. Accordingly, efforts to identify and correct the nutrient deficiencies that promote salt sensitivity hold promise for decreasing population risk of salt-induced hypertension without requiring reductions in salt intake. [ABSTRACT FROM AUTHOR]

On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/day, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤50 mmol/day up to 150 mmol/day or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt sensitivity. However, the new US dietary guidelines reduced the dietary potassium goal well below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension. [ABSTRACT FROM AUTHOR]

High salt intake is one of the major dietary determinants of hypertension and cardiovascular disease in Japan and throughout the world. Although dietary salt restriction may be of clinical benefit in salt-sensitive individuals, many individuals may not wish, or be able to, reduce their intake of salt. Thus, identification of functional foods that can help protect against mechanistic abnormalities mediating salt-induced hypertension is an issue of considerable medical and scientific interest. According to the “vasodysfunction” theory of salt-induced hypertension, the hemodynamic abnormality initiating salt-induced increases in blood pressure usually involves subnormal vasodilation and abnormally increased vascular resistance in response to increased salt intake. Because disturbances in nitric oxide activity can contribute to subnormal vasodilator responses to increased salt intake that often mediate blood pressure salt sensitivity, increased intake of functional foods that support nitric oxide activity may help to reduce the risk for salt-induced hypertension. Mounting evidence indicates that increased consumption of traditional Japanese vegetables and other vegetables with high nitrate content such as table beets and kale can promote the formation of nitric oxide through an endothelial independent pathway that involves reduction of dietary nitrate to nitrite and nitric oxide. In addition, recent studies in animal models have demonstrated that modest increases in nitrate intake can protect against the initiation of salt-induced hypertension. These observations are: (1) consistent with the view that increased intake of many traditional Japanese vegetables and other nitrate rich vegetables, and of functional foods derived from such vegetables, may help maintain healthy blood pressure despite a high salt diet; (2) support government recommendations to increase vegetable intake in the Japanese population. [ABSTRACT FROM AUTHOR]