Experimental induction of salt-sensitive hypertension is associated with lymphocyte proliferative response to HSP70.
Renal tubulointerstitial inflammation is a constant feature of experimental models of hypertension and likely plays a role in the pathogenesis of salt-sensitive hypertension. We have previously raised the possibility that the immune cell infiltration is driven by a low grade autoimmune reactivity directed to or facilitated by renal heat shock protein over expression. The present studies were done to gain insight on possible cell-mediated immune mechanisms in experimental hypertension by determining the renal expression of HSP70 and the proliferation index of T lymphocytes cultured with HSP70. We studied male Sprague-Dawley rats with inhibition of nitric oxide (NO) synthase (n=6), protein overload (PO) proteinuria (n=7) and short-term angiotensin II (Ang II) infusion (n=5), and their corresponding control groups. Each model was associated with 2 to 4 fold increase (P<0.05-0.001) in renal HSP70 expression. T cells isolated from the spleens demonstrated a significant two- to nine-fold response compared to controls (P<0.05 or lower for each comparison) when cultured with HSP70. These studies suggest that autoimmunity to stress proteins is involved in the sustained low-grade inflammatory infiltration that occurs in the tubulointerstitial areas of the hypertensive kidney.
Parra
Gustavo
G
Renal Service and Laboratory, Hospital Universitario and Universidad del Zulia, Maracaibo, Estado Zulia, Venezuela.
Quiroz
Yasmir
Y
Salazar
Jenny
J
Bravo
Yanauri
Y
Pons
Hector
H
Chavez
Maribel
M
Johnson
Richard J
RJ
Rodriguez-Iturbe
Bernardo
B
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011507:Proteinuria / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055049:Salt Tolerance / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology*
D018840:HSP70 Heat-Shock Proteins; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester