Hypertension (Dallas, Tex. : 1979) · 2026
Severe Acute Hypertension Causes Hemolysis With Release of PEP and ACE Inhibitor.
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Fischer Romy, Wysocki Jan, Hassler Luise, Batlle Daniel
Аннотация
BACKGROUND: Acute hypertensive crises can induce intravascular hemolysis, but its impact on the renin-angiotensin system remains unclear.
METHODS: Acute blood pressure elevations were induced in wild-type and PEP (prolyl endopeptidase)-deficient mice via Ang II (angiotensin II) injections. Systolic blood pressure, hemolysis index, and plasma enzymatic activities were evaluated. Native and cryo-hemolyzed plasma samples were incubated ex vivo with Ang II, with or without a PEP inhibitor, and Ang-(1-7; angiotensin-[1-7]) formation was measured over time. Ang II formation from Ang I (angiotensin I) was also assessed ex vivo. Plasma ACE (angiotensin-converting enzyme) protein levels were determined by Western blotting.
RESULTS: Ang II-induced blood pressure elevations led to hemolysis and a ~3.5-fold increase in plasma PEP activity, while the activities of other Ang II-degrading enzymes were unchanged. Pretreatment with recombinant ACE2 before Ang II infusion markedly attenuated both the systolic blood pressure and the hemolysis index. Cryo-hemolyzed plasma from mice and humans showed markedly increased ex vivo Ang-(1-7) formation from Ang II compared with native plasma, which was obliterated by PEP inhibition. In addition, ex vivo Ang II formation from Ang I was markedly decreased in cryo-hemolyzed plasma, and this was associated with reduced ACE activity, while ACE protein levels remained unchanged.
CONCLUSIONS: Acute severe hypertension induced by Ang II infusion causes intravascular hemolysis associated with increased plasma PEP activity and decreased plasma ACE activity that, based on ex vivo findings, enhance Ang II degradation to form Ang-(1-7) and reduce Ang II formation from Ang I, respectively. These previously unrecognized effects of hemolysis on renin-angiotensin system enzymes may be involved in mechanisms that influence acute blood pressure responses.
METHODS: Acute blood pressure elevations were induced in wild-type and PEP (prolyl endopeptidase)-deficient mice via Ang II (angiotensin II) injections. Systolic blood pressure, hemolysis index, and plasma enzymatic activities were evaluated. Native and cryo-hemolyzed plasma samples were incubated ex vivo with Ang II, with or without a PEP inhibitor, and Ang-(1-7; angiotensin-[1-7]) formation was measured over time. Ang II formation from Ang I (angiotensin I) was also assessed ex vivo. Plasma ACE (angiotensin-converting enzyme) protein levels were determined by Western blotting.
RESULTS: Ang II-induced blood pressure elevations led to hemolysis and a ~3.5-fold increase in plasma PEP activity, while the activities of other Ang II-degrading enzymes were unchanged. Pretreatment with recombinant ACE2 before Ang II infusion markedly attenuated both the systolic blood pressure and the hemolysis index. Cryo-hemolyzed plasma from mice and humans showed markedly increased ex vivo Ang-(1-7) formation from Ang II compared with native plasma, which was obliterated by PEP inhibition. In addition, ex vivo Ang II formation from Ang I was markedly decreased in cryo-hemolyzed plasma, and this was associated with reduced ACE activity, while ACE protein levels remained unchanged.
CONCLUSIONS: Acute severe hypertension induced by Ang II infusion causes intravascular hemolysis associated with increased plasma PEP activity and decreased plasma ACE activity that, based on ex vivo findings, enhance Ang II degradation to form Ang-(1-7) and reduce Ang II formation from Ang I, respectively. These previously unrecognized effects of hemolysis on renin-angiotensin system enzymes may be involved in mechanisms that influence acute blood pressure responses.