Mukul Ganguli

High potassium diets protect against dysfunction of endothelial cells in stroke-prone spontaneously hypertensive rats.

Two lines of evidence strongly support the hypothesis that high potassium diets protect arterial endothelial cells from hypertensive damage. Stroke-prone spontaneously hypertensive rats (SHRSP) fed normal (0.75%) K or high (2.1%) K and normotensive Wistar-Kyoto rats (WKY) were examined in an endothelial function study and a histological study. In the endothelial function study, aortic rings were suspended in tissue baths to monitor isometric tension. Rings contracted with norepinephrine were tested with acetylcholine and sodium nitroprusside. In normal K SHRSP (blood pressure, 156 mm Hg), endothelium-dependent acetylcholine relaxation was severely depressed by 49% (p < 0.001), whereas in high K SHRSP (blood pressure, 155 mm Hg), normal values were preserved. Endothelium-independent nitroprusside relaxation was virtually the same in both the SHRSP groups (high K vs normal K diet). Since indomethacin did not improve the impaired acetylcholine relaxation in normal K SHRSP, the cyclooxygenase products do not appear to have affected the endothelium-dependent relaxation in the normal K SHRSP. Thus, the endothelium-dependent relaxation response was much decreased in the normal K SHRSP and was preserved in the high K SHRSP. Thus, a high K diet appears to protect the aortic endothelium from a hypertension-induced dysfunction. In the histological study, aortic and mesenteric intimal lesions were assessed blindly under the microscope and graded from 0 to 60 for aortic and from 0 to 40 for mesenteric lesions. Aortic intimal lesion scores were 28 in normal K SHRSP (blood pressure, 209 mm Hg) and 13 in high K SHRSP (blood pressure, 207 mm Hg; −54%; p < 0.001). Mesenteric scores were 18 in rats on the normal K diet and 10 in rats on the high K diet (−45%; p < 0.001). Scores of high K SHRSP equaled those of WKY. Thus, a high K diet prevented the hypertensive intimal lesions without lowering the blood pressure. Endothelium protection by a high K diet seems a very likely partial explanation for the markedly reduced lesions in the high K SHRSP.

Prostaglandin E2 (PGE2) in renal papilla in NaCl hypertension

Human essential hypertension is clearly dependent on sodium intake and excretion.1 This “sodium connection” stimulated us to investigate prostaglandin E2 (PGE2) in the renal papillae of two strains of rats, the Dahl S strain, which is highly susceptible to salt-induced hypertension, and the Dahl R strain, which is highly resistant to salt hypertension.2 As seen in Fig. 1, when both strains are on a low-salt diet with 0.3% NaC1, neither strain has blood pressures (BPs) out of the normal range; however, when the two strains begin eating a high salt intake of 4% NaC1, the R strain has no rise of BP at all, while the S strain becomes mildly hypertensive at 4 weeks and solidly hypertensive by 11 weeks.

THE INFLUENCE OF RENAL PROSTAGLANDINS, CENTRAL NERVOUS SYSTEM AND NaCl ON HYPERTENSION OF DAHL S RATS

1.Kidney factors and central nervous system (CNS) factors appear to have powerful influences on NaCl‐induced hypertension. In quick‐frozen kidneys the prostaglandin E2 (PGE2) concentration in the renal papilla is 60% lower in Dahl S rats than in Dahl R rats (17 ng/100 mg vs 42 ng/100 mg; P<0.01) when both S and R rats are on a 0.3% low NaCl diet. When S and R rats eat a 4% high NaCl diet for 4 weeks or 11 weeks, the PGE2 concentration doubles in both strains (P<0.05) but the papillary PGE2 concentration in the S rats is always about half that in the R rats (P<0.01).

In SHR rats, dietary potassium determines NaCl sensitivity in NaCl-induced rises of blood pressure

The current study tested whether the spontaneously hypertensive rats (SHR) from Charles River Laboratories are resistant or not to NaCl-induced rises of blood pressure and deaths. These rats are fairly NaCl-resistant on a 2.1% high K diet, whereas they are quite susceptible to NaCl-induced hypertension and deaths on a 0.5% normal K diet. Thus, a high K diet strongly protects against a NaCl-induced rise of blood pressure as well as deaths in these SHR rats. Hence the level of dietary K determines the degree of NaCl sensitivity in these SHR rats.

Regulation of Plasma Flow and Other Functions of the Renal Papilla in Hypertension

Following the demonstration of a countercurrent multiplier system within the renal medulla as a mechanism for urinary concentration, a great deal of attention has been focused on the importance of the medullary circulation in the concentrating process and on the factors affecting this part of the renal circulation (Hargitay and Kuhn, 1951; Wirz et al., 1951).

Acute prostaglandin reduction with indomethacin and chronic prostaglandin reduction with an essential fatty acid deficient diet both decrease plasma flow to the renal papilla in the rat

Renal distribution of prostaglandin synthetase is mainly medullary, whereas the major degrading enzyme, prostaglandin dehydrogenase is primarily cortical. This suggests that prostaglandins (PG) released from the renal medulla could affect the medullary blood vessels. In two different experiments we studied the role of PG in the regulation of renal papillary plasma flow in the rat. First study: PG synthesis were stimulated in 34 adult Sprague-Dawley rats by bleeding from the femoral artery 1% of the body weight over a period of 10 minutes. Following this, indomethacin (a PG inhibitor, 10 mg/kg i.v.) was given slowly and then renal papillary plasma flow was measured 25 minutes after the end of infusion. In 17 indomethacin rats the renal papillary plasma flow averaged 18.8 ml/100 g/minute, whereas it averaged 23.0 in 17 non-indomethacin rats given diluent, an 18% reduction (p less than .025). Second study: Male Sprague-Dawley rats were made prostaglandin deficient by fasting rats for one week, followed by 10% dextrose fluid for one week and subsequent institution of an essential fatty acid (EFA) deficient diet for two weeks. With urinary PG excretion in prostaglandin deficient rats 28 ng/24 hours compared to 149 ng in control rats, they could be considered as prostaglandin deficient. When renal papillary plasma flow was measured, the 16 prostaglandin deficient rats had a 16% lower papillary plasma flow than 16 control rats, 21.6 vs 25.6 (p less than .005). These results clearly demonstrate that PG inhibition in rats decreases plasma flow to the papilla, strongly suggesting that PG are vasodilators for the vessels supplying the renal papilla.