UC San Diego

Hypertension is a major risk factor for cardiovascular disease, kidney failure and stroke. Recently, increasing evidences suggest a strong association between inflammation and hypertension. On the other hand, NF kappaB is a common transcription factor involved in inflammatory response and overexpressed in different end- organ damage. The objective of this study is to examine the role of NF kappaB in hypertension. NF kappa B expression level and translocation were compared between Wistar Kyoto rat (WKY) and spontaneously hypertensive rat (SHR) kidney, heart and brain. In addition, the animals were treated with a NFkappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), for ten weeks. To determine the correlation between NF kappaB and MMP, MMP-2 and -9 activities were examined after treatment. Immunohistochemistry results showed that NF kappaB expression level is significantly increased in SHR in renal glomerular and tubulointerstitial areas and brain hypothalamus compared to that in WKY (p <0.05), but not in myocardium and cerebral cortex. Significant NF kappaB translocation into the nucleus was found in renal tubular cells, cardiac muscle cells, and arterioles of kidney and brain in SHR. After PDTC treatment, the systolic blood pressure was suppressed in SHR by 36 %. NF kappaB expression level in treated-SHR was also decreased in renal glomerular and tubulointerstitial areas and hypothalamus compared to non-treated animals (p <0.05). Also, MMP-2 and -9 activities were reduced by PDTC in SHR after treatment. The higher MMP-9 activity in SHR was also significantly decreased by PDTC (p <0.01). These results suggest NF kappaB is an important factor in hypertension and may be responsible for MMP activity