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

Abstract

Objective: 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. Methods: Zymographic and digital immunohistochemical measurements in SHR pancreas and intestine were obtained as part of the digestive system with high levels of degrading enzymes. Objective: 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). Conclusions: 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.

In Vivo Diuretic Activity and Anti-Hypertensive Potential of Hibiscus sabdariffa Extract by Inhibition of Angiotensin-Converting Enzyme and Hypertension Precursor Enzymes

“…In addition, acidic amino acids (Asp and Glu) can chelate zinc atoms, which are cofactors of ACE [31]. This study confirms the hypotensive and anti-hypertensive effects of the Bowman-Birk protease inhibitor, particularly inhibiting trypsin and chymotrypsin [32]. This property contributes to the bioavailability of peptides with ACE inhibitory activity [33].…”

Polyphenol-Rich Extract from Litchi chinensis Seeds Alleviates Hypertension-Induced Renal Damage in Rats

“…Oxidative stress, a phenomenon of the imbalance of oxidation and antioxidation, would result from a variety of diseases or environmental stimuli, such as hypertension. , ROS is the most important marker of oxidative damage which could be activated by ET-1 . Excessive ROS attacks polyunsaturated fatty acids in the cell membrane through lipid peroxidation to generate MDA, which is regarded a common biomarker for in vivo oxidative stress and a bioactive trigger for inflammation .…”

Pancreatic Microcirculation Profiles in the Progression of Hypertension in Spontaneously Hypertensive Rats

“…Recently, it has been demonstrated that uncontrolled proteolytic receptor cleavage occurs in microcirculation in hypertension patients, leading to cellular and systemic dysfunction and even end-organic damage. 8–10 It has been proven that the pancreas serves as a major systemic major source of digestive enzymes (mainly serine proteases, 11 such as matrix metalloproteinases 12 , 13 and trypsin 14 ) in the microcirculation and surrounding tissues, 15 which may be one of the explanations underlying enhanced protease activity in SHRs 16 and the generated pathophysiological response of clinical manifestations observed in hypertensive individuals. These lines of evidence highlight the importance of pancreatic microcirculation in the development of hypertension.…”