SUMMARY In metabolic balance studies the intake and excretion of sodium, potassium, and water were measured in spontaneously hypertensive rats (SHRs) of the Okamoto-Aoki strain and agematched Wistar Kyoto rats (WKYs) that were 3 through 13 weeks of age. While fed their usual chow, young SHRs exhibited differences in excretion as compared to WKYs consuming essentially equivalent amounts of food and water. Fractional sodium and water excretion (percent of amount ingested) by SHRs were significantly less during Weeks 4-6 and 6-7, respectively, due to lower rates of urinary excretion. Potassium excretion was less in SHRs at 4-5 weeks. These observations indicate that SHRs retain more urinary sodium, potassium, and water during an early phase of hypertension than normotensive, age-matched WKYs. After 8 weeks of age, fractional excretion of electrolytes and water did not differ appreciably between strains.In another group of rats, sodium intake was restricted and observations were made from 3 through 13 weeks of age. Although SHRs excreted slightly less sodium, cumulative sodium balance was similar in SHR and WKY. Sodium restriction slowed the increase in arterial pressure in SHRs younger than 9 weeks of age and reduced the magnitude of the hypertension in 10-through 13-week-old SHRs. At the latter age, arterial pressure was not as high in sodium-restricted SHR as in SHR on the standard sodium diet, but it was elevated above that in either WKY groups. Thus dietary sodium restriction retards the development, but does not prevent the hypertension in SHR. (Hypertension 4: 908-915, 1982) KEY WORDS • hypertension sodium restriction blood pressure • kidney • sodium excretion A LTHOUGH animals with genetic or spontaneous hypertension have been studied extensively to ascertain the mechanisms initiating and maintaining hypertension in humans, our understanding of the etiology of this complex, polygenic or multifactoral disorder is incomplete. Of the several basic mechanisms that may be involved, one proposal centers on a reduced capacity of the kidneys to excrete salt and water in proper relation to intake.1 Some function of sodium metabolism appears to be important in the pathogenic process in the Okamoto-Aoki strain of spontaneously hypertensive rats (SHR) since chronic consumption of excess sodium chloride augments, whereas sodium restriction generally attenuates the hypertension.2 "* In addition, cross-transplantation studies indicate that a defect in renal function plays an important role in determining the level of arterial pressure. 5 -6 Previous balance studies 7 -8 examining urinary excretion over a 1 -or 3-week period provide evidence of renal dysfunction in young genetically hypertensive rats of the Milan strain (MHS) and stroke-prone substrain of SHR (SHRSP). Similar results were recently reported by Herlitz et al.9 for 7-week-old SHR as compared with normotensive Wistar rats; however, no data were presented for the appropriate genetic control, WKY.In the present balance study, we assessed renal excretion by ...

Renal and nephron hemodynamics were compared between anesthetized, nondiuretic, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although the mean arterial pressure was higher in SHR than in WKY, 158 VS. 114 mmHg, glomerular filtration rate (GFR) and renal blood flow (RBF) were similar in both groups. So were intrarenal hydrostatic pressures, single nephron GFR (SNGFR), and single nephron blood flow (SNBF). Accordingly, the increased renal vascular resistance (RVR) in SHR was due to predominant preglomerular vasoconstriction. In a second group of SHR, SHR-AC, the femoral arterial pressure was reduced acutely to 114 mmHg by means of aortic constriction above the renal arteries. The mean values for GFR, RBF, SNGFR, SNBF, and intrarenal hydrostatic pressures resembled those in SHR, whereas RVR was less in SHR-AC. These autoregulatory adjustments of RVR were again largely limited to the preglomerular vasculature. Efferent arteriolar resistance was similar in all three groups. We conclude that the enhanced RVR in 12-wk-old SHR is primarily a consequence of a physiological, autoregulatory response of afferent arteriolar resistance to the elevated arterial pressure. Further, RVR in SHR is not fixed and constant but responds appropriately to reductions in renal perfusion pressure.

We characterized renal tubular reabsorption before and during acute expansion in anesthetized 12-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although mean arterial pressure was higher in euvolemic, nondiuretic SHR than in WKY, 158 vs. 114 mmHg, kidney and nephron glomerular filtration rate (GFR) as well as fluid reabsorption by the proximal convoluted tubule, loop of Henle, and distal convoluted tubule-collecting duct were similar. In euvolemic SHR with aortic constriction (SHR-AC), an acute decrease in renal perfusion pressure to 114 mmHg reduced sodium and water excretion. Kidney and nephron GFR and fluid reabsorption by segments along the nephron resembled values for SHR and WKY. Infusion of isotonic saline (3 ml.100 g body wt-1.h-1) produced similar increases in fractional sodium and water excretion by SHR and WKY, whereas SHR-AC exhibited a blunted natriuresis and diuresis. During expansion, fluid reabsorption by the nephron segments did not differ appreciably among the three groups. The effect(s) of perfusion pressure on reabsorption by superficial nephrons may be covert and was not unmasked, or may be manifested preferentially by deeper nephrons. We conclude that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.

Previous investigations have provided evidence that the activity of parasympathetic efferent neurons in the dorsal motor nucleus of the vagus (DMNV) may be influenced by either vagal afferent or spinal input from the gastrointestinal (GI) tract. Many questions remain, however, regarding the nature of this input and its integration by the brain stem. The present study was designed to examine one important aspect of this issue: the potential contribution of the spinal input to the brain stem in the generation of the response properties of intestine-sensitive neurons in the DMNV. Using intracellular recording and labeling techniques in adult rats, we found that ascending spinal pathways were capable of conveying both low- and high-threshold visceral information to the DMNV. We also determined that the neurons in the nucleus of the solitary tract failed to respond to intestinal distention when the vagal afferents to the brain stem had been severed, suggesting that the spinal projections terminate directly on the DMNV neurons. These data lend support to the emerging hypothesis that the spinal afferents that accompany the abdominal splanchnics are capable of responding to both innocuous and noxious stimuli. The results also suggest that the neurons in the DMNV play a larger role in the integration of visceral sensory information than was previously realized.

Renal glomeruli were isolated from rat kidneys using a passive mechanical sieving technique. Glomerular microsomal fraction, glomerular homogenate, or intact glomeruli were incubated with [1-14C]arachidonic acid, and the profile of prostaglandin (PG) synthesis was determined by thin-layer chromatography. The three incubation systems produced 15.3, 20.8, and 40.4% 6-keto-PGF1 alpha; 19.1, 23.5, and 15.3 PGF2 alpha; 5.7, 9.1, and 3.9% thromboxane (TX) B2; 36.0, 35.1, and 37.0% PGE2; and 23.9, 11.3, and 3.4% PGD2, respectively. Glomeruli were placed in suspension within glass chambers and superfused with Krebs solution. Superfusion with 1.6 x 10(-4) M arachidonic acid stimulated a significant release of renin from glomeruli, whereas 2.7 x 10(-6) M PGE1, PGE2, PGF2 alpha, TXB2, PGD2, or a stable analog of PGH2 had no effect on renin. When the rapid breakdown of PGI2 was counteracted by either increasing the concentration to 1.7 x 10(-4) M or stabilizing in Krebs at pH 9.4, it stimulated a significant increase in renin release. Reducing the arachidonic acid concentration to 1.6 x 10(-5) M eliminated both renin release and PGI2 synthesis, while increased PGE2 synthesis persisted. Finally, using an inhibitor of PGI2 synthesis, azo analog 1 (2.8 x 10(-6) M), 6-keto-PGF1 alpha produced in response to arachidonic acid was eliminated, as was the concurrent release of renin, but PGE2 synthesis was not affected. These results suggest that the mechanism of direct interaction between renal PG and renin in isolated glomeruli is selectively due to the action of PGI2.