Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.

Objective— Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA 2 -IIA (group IIA secretory phospholipase A 2 ) plays an integral role in regulating vascular inflammation. Although studies investigated sPLA 2 -IIA in secondary prevention, we prospectively evaluated sPLA 2 -IIA mass and genetic variants with CVD events in a primary prevention population with chronic inflammation. Approach and Results— The JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) randomized participants with LDL (low-density lipoprotein) <130 mg/dL and hsCRP (high-sensitivity C-reactive protein) ≥2 mg/L to high-intensity rosuvastatin versus placebo. Baseline and 1-year plasma sPLA 2 -IIA mass was measured (N=11 269 baseline; N=9620 1 year). We also identified genetic variants influencing sPLA 2 -IIA using genome-wide association and examined them with CVD. Three hundred thirteen incident CVD events occurred during follow-up. Baseline sPLA 2 -IIA mass (median, 25th–75th percentile: 3.81, 2.49–6.03 ng/mL) was associated with increased risk of CVD: risk factor–adjusted hazard ratio (95% CI; P ) per SD increment: 1.22 (1.08–1.38; P =0.002). This remained significant (1.18; 1.04–1.35; P =0.01) after incrementally adjusting for hsCRP. Similar estimates were observed in rosuvastatin and placebo groups ( P treatment interaction>0.05). The rs11573156C variant in PLA2G2A (encoding sPLA 2 -IIA) had the strongest effect on sPLA 2 -II: median (25th–75th percentile, ng/mL) for CC and GG genotypes: 2.79 (1.97–4.01) and 7.38 (5.38–10.19), respectively; and had nonsignificant trend for higher CVD risk (hazard ratio, 1.11; 95% CI, 0.89–1.38; P =0.34). Conclusions— In the JUPITER population recruited on chronic inflammation, sPLA 2 -IIA mass was associated with CVD risk relating to vascular inflammation not fully reflected by hsCRP. Additional studies, including larger functional genetic and clinical studies, are needed to determine whether sPLA 2 -IIA may be a potential pharmacological target for primary prevention of CVD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.

Salt depleted rabbits and humans excrete an oral sodium load more quickly via the kidneys than an intravenous one. This has been ascribed to the presence of a sodium sensor in the gastrointestinal tract which in some way can influence renal function. The purpose of this study was to investigate this response in the Dahl rats. Renal and faecal sodium excretion was followed in the two strains of rats (normotensive, saltresistant (SR/Jr) and hypertensive, saltsensitive (SS/Jr) rats). After 4 days on a low salt diet they were given NaCl (1.5 mmol k(-1) body wt) either by gavage or intravenously. SR/Jr rats showed an increased renal sodium excretion both after oral and intravenous sodium repletion. The excretion was 2-3 times greater after th oral than after the intravenous administration. The SS/Jr rats augmented their renal sodium excretion only after the oral load, although the sodium excretion was significantly less than in SR/Jr rats. In fact, during the first 8 h after giving sodium orally the renal excretion of sodium was on an average eight times larger in the SR/Jr than in the SS/Jr rats. Renal excretion of sodium was similar in the two strains after intravenous administration. We conclude that the hypertensive SS/Jr rats have great difficulties in excreting an oral sodium load, a phenomenon that may be of importance in the pathophysiology of arterial hypertension in this strain of rats.

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin-angiotensin-aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, inbred hypertension-prone (SS/Jr) and hypertension-resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three- to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin-angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.

Small intestine of cat was homogenized under denaturing condition (6.0 M guanidinium chloride) in the presence of protease inhibitors and molecules in the 500 to 10,000 Da mass range were obtained by sequential ultrafiltrations. This material was separated by gel chromatography (Sephadex G-25), where fractions eluted in the mass range of 500-1000 Da inhibited 86Rb uptake into kidney slices in vitro. Furthermore, the same fractions exhibited a natriuretic effect when given intravenously to anesthetized rats. The gel chromatography fractions were further purified by cation exchange chromatography (CM-Sephadex C-25). Fractions eluted with a NaCl solution of around 250 mM inhibited 86Rb uptake into renal cortical tissue in vitro and showed natriuretic activity when tested in vivo in rats. It is proposed that intestine contains a water soluble natriuretic factor with an apparent molecular mass of 500-1000 Da. This material evokes a natriuresis in vivo and inhibits 86Rb uptake in vitro.