Glomerular basement membrane polyanion distribution and nitric oxide in spontaneous hypertensive rats: Effects of salt loading and antihypertensive therapy with propranolol

Cationic colloidal gold (CCG), a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanio ns, mainly heparan sulfate proteoglycan in spontaneous hypertensive rats (S HR) with or without salt loading and antihypertensive treatment with propra nolol. The changes of mean GBM width and anionic sites distribution were as sessed by electron microscopy. Plasma and urinary nitrates (NOx) were measu red by nitrite (NO2) + nitrate (NO3), stable metabolites of NO, SHR had dec reased NO production and increased GEM width (27%) compared with the contro l Wistar-Kyoto (WKY) rats. The chronic high dietary salt intake resulted in a significant increase in blood pressure, proteinuria, and renal function in the SHR rats. The chronic high salt dietary intake resulted in a decreas e in NO in the WKY and a further reduction in NO production in the SHR, The GBM anionic sites count was similar in the SHR and WKY nonsalt-loaded grou ps, 13.5 +/- 0.5 and 12.8 +/- 0.4 CCG counts/mu m GBM, respectively, but si gnificantly lower in both salt-loaded SHR and WKY, 9.9 +/- 0.55 (P < .01) a nd 9.6 +/- 0.55 (P < .01) CCG counts/mu m GBM, respectively. Antihypertensi ve treatment with propranolol in the salt-loaded SHR group resulted in lowe r blood pressure, a further decrease in NO production, but no significant c hanges in GBM width and anionic sites count. It is concluded that chronic h igh salt intake may be deleterious to the permselectivity of the GBM. A low NO production state that results from chronic salt loading in already hype rtensive rats will result in more severe organ (renal) damage, most probabl y by the addition of the loss of GBM permselectivity to the existing pathom orphologic changes. (C) 2000 American Journal of Hypertension, Ltd.