Loss of endothelium and receptor-mediated dilation in pial arterioles of rats fed a short-term high salt diet

A high salt diet often is regarded as an accessory risk factor in hypertens ion, coincidental to the deleterious effect of high blood pressure on vasod ilator function. The aim of this study was to determine whether short-term ingestion of a high salt diet per se impairs vasodilator function in the ce rebral circulation independent of blood pressure changes. Adult Sprague-Daw ley rats were fed a normal salt (0.8%) or high salt (4%) diet for 3 days. M ean arterial pressures were similar in the normal and high salt groups (123 +/- 2 and 125 +/- 2 mm Hg, respectively). Subsequently, the responses of t he in situ pial arterioles to acetylcholine. iloprost, and sodium nitroprus side were determined in cranial windows using intravital videomicroscopy. P ial arterioles of rats fed normal and high salt diets showed similar restin g diameters of 69 +/- 2 and 72 +/- 3 mu m, respectively, but their reactivi ty patterns to vasodilator stimuli were markedly different. Arterioles of r ats fed a normal salt diet dilated progressively up to 17 +/- 3% in respons e to the endothelium-dependent agent acetylcholine (10(-9) to 10(-6) mol/L) and dilated by 22 +/- 2% in response to the prostaglandin I-2 receptor ago nist iloprost (3 X 10(-11) mol/L), In contrast, pial arterioles of rats fed a high salt diet constricted by 4 +/- 3% and 8 +/- 2% in response to acety lcholine and iloprost, respectively. Sodium nitroprusside (10(-6) mol/L), a nitric oxide donor, dilated pial arterioles of rats fed low and high salt diets by a similar amount (19 +/- 3% and 16 +/- 2%, respectively), suggesti ng that signaling mechanisms for dilation distal to the vascular smooth mus cle membrane were intact after high salt intake. These results provide the first evidence that the short-term ingestion of a high salt diet may severe ly impair the vasodilator function of the in situ cerebral microcirculation independent of blood pressure elevation.