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) polyanions, mainly heparan sulfate proteoglycan in spontaneous hypertensive rats (SHR) with or without salt loading and antihypertensive treatment with propranolol. The changes of mean GBM width and anionic sites distribution were assessed by electron microscopy. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO2) + nitrate (NO3), stable metabolites of NO. SHR had decreased NO production and increased GBM width (27%) compared with the control 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 decrease 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 groups, 13.5 +/- 0.5 and 12.8 +/- 0.4 CCG counts/microm GBM, respectively, but significantly lower in both salt-loaded SHR and WKY, 9.9 +/- 0.55 (P < .01) and 9.6 +/- 0.55 (P < .01) CCG counts/microm GBM, respectively. Antihypertensive treatment with propranolol in the salt-loaded SHR group resulted in lower blood pressure, a further decrease in NO production, but no significant changes in GBM width and anionic sites count. It is concluded that chronic high salt intake may be deleterious to the permselectivity of the GBM. A low NO production state that results from chronic salt loading in already hypertensive rats will result in more severe organ (renal) damage, most probably by the addition of the loss of GBM permselectivity to the existing pathomorphologic changes.
Department of Nephrology, Ichilov Tel-Aviv, Israel.
S
S
Hertzan-Levy
E
E
Skutelsky
T
T
Arad
Y
Y
Wollman
T
T
Chernihovsky
S
S
Polak-Charcon
A
A
Iaina
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D005260:Female; D006046:Gold / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D000071228:Polyelectrolytes; D011107:Polylysine / Q000378:metabolism; D011108:Polymers / Q000378:metabolism*; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D006046:Gold; D009566:Nitrates; D009569:Nitric Oxide; D009573:Nitrites; D000071228:Polyelectrolytes; D011107:Polylysine; D011108:Polymers; D011433:Propranolol; C089532:cationic colloidal gold