Pancreatic source of protease activity in the spontaneously hypertensive rat and its reduction during temporary food restriction.

Abstract

The mechanisms underlying cell and organ dysfunctions in hypertension are uncertain. The spontaneously hypertensive rat (SHR) has elevated levels of unchecked degrading proteases compared to the control Wistar Kyoto (WKY) rat. The extracellular proteases destroy membrane receptors leading to cell dysfunctions, including arteriolar constriction and elevated blood pressure. Our goal was to identify potential sources of the uncontrolled enzymatic activity. Zymographic and digital immunohistochemical measurements in SHR pancreas and intestine were obtained as part of the digestive system with high levels of degrading enzymes. The results showed that SHRs have significantly higher protease activity than WKY in pancreas (22.04 ± 9.01 vs 13.02 ± 3.92 casein fluorescence intensity unit; P < 0.05) and pancreatic venules (0.011 ± 0.003 vs 0.005 ± 0.003 trypsin absorbance; P < 0.05) as well as in venous blood (71.07 ± 13.92 vs 36.44 ± 16.59 casein fluorescence intensity unit; P < 0.05). The enzymatic activity is contributed by trypsin and chymotrypsin. Furthermore, a decrease of these enzyme activity levels achieved during a short-term fasting period is associated with a reduction in systolic blood pressurein SHR (135 ± 8 mm Hg vs 124 ± 7 mm Hg; P < 0.05). The results suggest the pancreas of the SHR is a potential source for serine proteases leaking into the circulation and contributing to its protease activity.