Salt-induced hypertension in Dahl salt-sensitive rats. Hemodynamics and renal responses.

Abstract

This study was performed with Dahi salt-sensitive (DS) and Dahi salt-resistant (DR) rats to detect differences hi cardiovascular hemodynamics and renal responses that might be involved hi initiating salt-induced hypertension hi DS rats. The effects of 4 weeks of 8% NaCl diet were studied hi conscious, male DR and DS rats hi which vascular and urinary catheters had been previously implanted. Results were compared with those obtained from control groups of DR and DS rats on 4 weeks of 1% NaCl diet. DR rats on 8% salt diet did not develop hypertension, and cardiac output and blood volume were unchanged; glomerular filtration rate, urinary flow, sodium excretion, and plasma atrial natriuretic factor (ANT) increased. DS rats on 8% salt diet developed hypertension, and cardiac output and blood volume increased; glomerular filtration rate, urinary flow, and sodium excretion did not change, despite an increase hi ANF. DS and DR rats on 1% NaCl diet were subjected to ANF infusion. After ANF infusion DR rats had a decreased blood volume and an increased glomerular filtration rate, urinary flow, and sodium excretion; DS rats showed no significant changes hi blood volume, glomerular filtration rate, urinary flow, or sodium excretion. ANF caused vasodilation hi all regions studied hi DR rats; DS rats showed vasodilation hi all regions except the kidney. After acute volume expansion, although both DR and DS rats responded by an increase hi cardiac output, only DS rats developed prolonged hypertension. This finding suggests an inadequate vasodilatory mechanism in DS rats. In response to acute volume expansion, renal resistance decreased hi DR rats but not hi DS rats. It is concluded that the primary hemodynamic disturbance hi DS rats with salt-Induced hypertension is an increase hi cardiac output caused by blood volume expansion hi the absence of any vasodilation. Comparison of the responses of DS and DR rats to high salt diets, ANF infusion, and acute volume expansion indicates that the salt-induced hypertension in DS rats is initiated by a diminished renal response to ANF. (Hypertension 1989;13:612-621) T his study was performed with Dahi saltsensitive (DS) and Dahi salt-resistant (DR) rats to detect differences in cardiovascular hemodynamics and renal responses that might be involved in initiating salt-induced hypertension in DS rats. On the basis of experimental evidence as

Dual hemodynamic mechanisms for salt-induced hypertension in Dahl salt-sensitive rats.

“…At 4 and 8 weeks, DR rats on 8% NaCl had no statistically significant changes in TPR, CO, and BV. The 8% salt diet resulted in a significant expansion of BV (p <0.05) at 4 weeks (as previously reported 18 ) and 8 weeks in DS rats. At 4 weeks, DS rats on 8% NaCl had a marked increase in CO (p<0.05), whereas TPR was not significantly changed.…”

“…16 ' 17 We previously reported that hypertension that developed in DS rats in response to a high salt diet (8% NaCI) for 4 weeks resulted, at least partly, from an inability of the kidney to vasodilate and to increase sodium and water excretion; an expanded blood volume (BV) and an increased cardiac output (CO) were responsible for the hypertension. 18 According to Guyton et al, 19 in the presence of an increased CO and augmented tissue blood flow, total peripheral resistance (TPR) increases significantly with "long-term autoregulation" (i.e., vasoconstrictor regulation of tissue perfusion), and CO returns to normal; elevated TPR then becomes responsible for the hypertension.…”

The beta2 subunit inhibits stimulation of the alpha1/beta1 form of soluble guanylyl cyclase by nitric oxide. Potential relevance to regulation of blood pressure.

“…Increased renal vasculature resistance and reduced salt excretion have been determined in the Dahl salt-sensitive rat, and have been postulated to play a central role in the pathogenesis of hypertension (20,21). NO reduces renal vascular resistance, and increases sodium excretion (22,23).…”

Handling 22 NaCl by the Blood-Brain Barrier and Kidney

“…After a high NaCl diet, plasma and CSF volume expansion might obscure an increase in total sodium content if only sodium concentration is determined. We observed that after an 8% NaCl diet, hypertension in DS rats was initiated by blood volume expansion and increased CO but was perpetuated by increased TPR, 16 whereas prolonged ingestion of 1% NaCl caused hypertension by increasing TPR. 18 Conceivably, increased access of NaCl to the brain of DS rats may be responsible for the increased TPR.…”

“…An 8% NaCl diet causes rapid onset of severe hypertension initially because of blood volume expansion and elevated cardiac output (CO); however, CO rapidly returns to normal and hypertension is maintained by increased TPR, even though hypervolemia persists. 16,18 Our major objective was to determine how 22 NaCl is handled in prehypertensive DS and Dahl salt-resistant (DR) rats on a low NaCl (0.23%) diet before hemodynamic or structural abnormalities related to hypertension have occurred. Furthermore, we studied the effects of hypertension induced by 8% NaCl on the handling of 22 NaCl by the blood-brain barrier (BBB).…”