Effect of salt on prostaglandin metabolism in hypertension-prone and -resistant Dahl rats.

Abstract

SUMMARY The effect of high salt intake on rascular and renomedullary prostaglandin (PG) synthesis was compared in Sprague-Dawley and salt-sensitive (S) and -resistant (R) Dahl rats. Animals were given a diet containing either 0.6% or 8% NaCI starting at 5 weeks of age, and were sacrificed 6 weeks later. Systolic blood pressure of S rats increased to 220 ± 7 mm Hg but was unaffected in R and Sprague-Dawley rats. Prostaglandin synthesis was studied in aortic rings and renomedullary mlcrosomes using 14 C-arachidonate as substrate.[*H]PGE, degradation was measured in the renocortical cytosol.In Sprague-Dawley and R rats, aortic PGI t synthesis was not affected by high salt intake, while a significant increase compared to animals on 0.6% NaCI (from 608 ± 84 to 992 ± 108 pmoles/60 min, p < 0.05) was noted in S rats. Enhancement of PGI| synthesis in S rats may be secondary to the hypertension.Salt-loading consistently stimulated renomedullary PGE, synthesis in all three animal groups. S rats, however, had the lowest PG synthesis in renal medullas compared to Sprague-Dawley and R rats when placed on either diet. Thus, even after 6 weeks on high salt, S rats did not reach the levels of PGE, synthesis seen in R or Sprague-Dawley rats on regular diet.The activity of cortical 15-hydroxyprostaglandin dehydrogenase was increased by salt-loading in S and Sprague-Dawley, but not in R rats. R rats had lower dehydrogenase activity than the other two groups when placed on either diet.The observed differences in PG synthesis and catabolism will tend to maintain the net output of renal PGs highest in R and lowest in S rats. These differences correlate with the reported differences in renal papillary flow between these two rat strains and may be relevant to their susceptibility or resistance to hypertension in response to salt. Prostaglandins are involved in the • regulation of physiological and biochemical pathways through both sodium balance and vascular smooth muscle which genetic factors exert their influence on blood tone. It is possible that differences in the pattern of pressure (BP) are unclear. Because of the pivotal role renal and vascular prostaglandin metabolism mediate, of the kidney in regulating BP by maintaining sodium in part, the variable response of BP to salt. The study of the role of prostaglandins in salt-induced hypertension has been facilitated by the development of two From the Department of Pathology, Veterans Administration strains of rats, one sensitive (S) and one resistant (R)%S ^JX^$^ffi?^s£% t0 the effects of salt.-Induction of hypertension in S of Medicine, Minneapolis, Minnesota, and the Broolchaven r a t S by a high salt diet is associated with decreased National Laboratories, Upton, New York renal papillary flow, 10 decreased natriuretic capacity,' Supported in part by grants from the American Heart Assocmand increased systemic vascular resistance 7 compared tion, Minnesota Affiliate, and the Veterans Administration t Q R r a t s T h e p r e s e n t stu( Jy explores the possibility P a S S a -S l S...

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

“…8,9 It should be noted that such an activation of prostanoid formation was absent in prehypertensive SHRs 11,12 or in salt-sensitive Dahl rats fed on a low-salt diet. 8,9 This result suggests that prostanoid synthesis is enhanced as a consequence of high BP and/or underlying hypertensive mechanisms. In addition, the acute COX inhibition by indomethacin increased the vascular resistance in perfused SHRs' hindlimbs.…”

“…It seems that the magnitude of the BP response to acute inhibition of NO synthase by N G -nitro-L-arginine methyl ester (L-NAME) injection is preserved in both salt and spontaneous hypertension, 1,4 but NO-dependent vasodilatation is clearly insufficient in compensating for major sympathetic hyperactivity, indicating a relative NO deficiency in rats with these forms of hypertension. 6,7 The synthesis and/or release of vasodilator prostanoids (namely prostacyclin (PGI 2 )) has been found to be increased in the blood vessels of Dahl salt-hypertensive (DS-HS) rats, 8,9 DOCA-salt hypertensive rats and spontaneously hypertensive rats (SHRs), 10,11 but not in prehypertensive SHRs. 11,12 Few attempts have been made to evaluate the contribution of these prostanoids to BP regulation.…”

Roles of Renal Cytochrome P450-Dependent Arachidonic Acid Metabolites in Hypertension.

“…However, the salt sensitivity can be transferred from S to R animals by the transplantation of a S strain kidney (Dahl et al 1974), suggesting the kidney plays a major role in this model of hypertension. Urinary excretion (Sustarsic et al 1981), renal papillary levels (Tobian et al 1982) and renomedullary synthesis of prostaglandin E2 (Limas et al 1981) are reported to be lower in S than in R rats. However, there are no available data about the characteristics of renal cytochrome P450 arachidonate metabolites in Dahl rats.…”

Papillary collecting tubule synthesis of prostaglandin E2 in Dahl rats.

“…7 The PGEj content of snap-frozen renal papillae was also less in the DS than in the DR, both before and after high salt diets. 8 Renal medullary microsomes from DS also underproduced PGEj as compared with microsomes from DR. 9 Reduction of medullary PGEj may be important in the defective natriuresis observed in the DS strain. Prostaglandins have a role in promoting natriuresis in the inner medullary collecting duct in volume-expanded rats, 10 a situation somewhat analogous to high salt feeding.…”