Body fluid expansion is not essential for salt-induced hypertension in SS/Jr rats

Abstract

To evaluate the importance of volume in the development of hypertension in inbred Dahl salt-sensitive rats (SS/Jr), we measured the changes in blood pressure (BP) that occurred with oral intake of food (salt) and water in rats whose body weight was permitted to increase versus those in which body weight was maintained constant with a servo-control system. We hypothesized that if volume expansion is essential in the development of hypertension, then BP would not increase if body weight was held constant. We found that oral presentation of chow containing 4% salt to SS/Jr rats caused BP to increase 32.2 +/- 2.9 mmHg over 4 days when body weight was controlled at its initial value. Plasma sodium increased from 142.0 to 145.2 meq/l during 4 days of high salt. Neither plasma volume, hematocrit, nor central venous pressure changed significantly on the high-salt diet. In contrast, the inbred Dahl salt-resistant rats (SR/Jr) did not increase their BP during body weight control when given 4% salt. This demonstrates that volume expansion is not an obligatory step in the pressure response to increased salt in SS/Jr rats. Our results obtained with oral presentation of salt, in contrast to intravenous, represent a physiological evaluation of the significance of volume changes in response to dietary salt because no potential regulatory reflexes have been bypassed.

Sodium-Selective Salt Sensitivity

“…This observation suggests that, in some sult-sensitive humans, the plasma concentration of Na ϩ attained with Na ϩ loading may critically determine the extent of the pressor effect of dietary NaCl. The observation accords with observations that Qi et al 21 reported in the NaCl-loaded Dahl SS/Jr rat, in which BP varied directly and highly significantly with plasma Na ϩ concentration, irrespective of the hydration state orally imposed. Qi et al 21 proposed, as have others, 4,22,23 that "directly mediated increases in plasma Na ϩ can increase arterial BP in rats by mechanisms that are apparently not related to fluid volume changes."…”

“…The observation accords with observations that Qi et al 21 reported in the NaCl-loaded Dahl SS/Jr rat, in which BP varied directly and highly significantly with plasma Na ϩ concentration, irrespective of the hydration state orally imposed. Qi et al 21 proposed, as have others, 4,22,23 that "directly mediated increases in plasma Na ϩ can increase arterial BP in rats by mechanisms that are apparently not related to fluid volume changes." An increase in plasma Na ϩ concentration may elicit a pressor effect by increasing cerebro-spinal fluid Na ϩ concentration 24 and by thereby activating central sympathoexcitatory mechanisms that give rise to increased sympathetic outflow.…”

“…An increase in plasma Na ϩ concentration may elicit a pressor effect by increasing cerebro-spinal fluid Na ϩ concentration 24 and by thereby activating central sympathoexcitatory mechanisms that give rise to increased sympathetic outflow. 21,[25][26][27] In SS but not in SR subjects, NaHCO 3 , as well as NaCl loading, induced a clear-cut reduction in RBF and, hence, a robust increase in RVR, a phenomenon described previously only with NaCl loading in sult-sensitive humans, 28,29 including normotensive blacks. 19 Clearly, the Cl Ϫ component of NaCl is not required to elicit this dysfunctional renal hemodynamic response to Na ϩ loading.…”

“…33,34 In some instances of salt sensitivity, initiation of the pressor effect of dietary NaCl would appear to require something beyond, or other than, an abnormally enhanced renal retention of its ionic components and their complimentary osmotic capacities to expand PV, 20,33,34 possibly an increase in plasma Na ϩ that elicits an increased central nervous system sympathetic outflow. 4,[21][22][23]25,27 Accordingly, the current observations expand the scope of possible pathogenic mechanisms of human hypertension and, hence, the scope of its potential treatment and prevention.…”

The time course of salt-induced hypertension, and why it matters

“…Herein, we refer to salt-induced changes of this time course as 'acute' to distinguish them from much slower salt-induced effects discussed in subsequent sections. Acute salt sensitivity of blood pressure has been demonstrated in experiments involving a number of species including chickens, 19,20 dogs, [21][22][23][24] green monkeys, 25 mice, 26 pigs, 27 rabbits, 28,29 rats [30][31][32][33][34] and spider monkeys. 25,35 An example of the time course of the blood pressure response to a high-salt diet in regular Sprague-Dawley rats is shown in Figure 2.…”