Circulating Aminopeptidase Activities in Men and Women with Essential Hypertension

Abstract

Essential hypertension is one of the major contributors to premature morbidity and mortality due to the incresased risk for coronary heart disease, stroke, renal disease, peripheral vascular disease and vascular dementia for both men and women. However, its basic causes remain unknown. In the present work we studied the activity of several proteolytic regulatory enzymes related to renin-angiotensin-system (RAS) (aminopeptidase A, APA; aminopeptidase N, APN; aminopeptidase B, APB; and insulin-regulated aminopeptidase, IRAP); with oxytocin regulation (oxytocinase); with the metabolism of GnRH and TRH (pyrrolidone carboxypeptidase, Pcp); and with enkephalins metabolism (enkephalindegrading activity, EDA), to elucidate their role in the mechanisms responsible of essential hypertension and to discuss the possible gender differences. Serum samples of 53 individuals with essential hypertension and 60 healthy volunteers were collected and used to assay enzyme activities, gonad hormones testosterone and estradiol, TSH and free thyroxin (fT4). Differences were observed in APA, APN, Pcp and EDA specific activities, and in serum gonad hormone levels between hypertensive and control groups. Only Pcp activity showed gender differences. Regarding the RAS, APA is reduced while APN is increased, suggesting increased levels of angiotensin II and a facilitation of the conversion of angiotensin III in angiotensin IV. Thus, the changes in several RAS-regulating specific activities and other enzyme activities involved in the neuroendocrine modulation of gonad and stress-related functions are related to essential hypertension with minor gender differences. Therefore, aminopeptidases constitute new elements for the knowledge of the causes of essential hypertension and an alternative as therapeutic targets against the illness.

Sex differences in the aging pattern of renin–angiotensin system serum peptidases

“…In fact, androgens can stimulate RAS [ 33 ], and the sexually dimorphic pattern of hypertension in the spontaneously hypertensive rat is androgen-dependent, rather than estrogen-dependent [ 34 ]. Accordingly, serum peptidases, such as ACE, ACE2, NEP, APN, and APA, which are important elements of the RAS, were studied here because dysregulation of these enzymes has been associated with hypertension and cardiovascular risk [ 35 ]. Our results revealed sexual differences in these activities, with a different pattern in pre- and post-andropausal/post-menopausal subjects.…”

Bioinformatics identification of potential candidate blood indicators for doxorubicin‑induced heart failure

“…ANPEP is a conserved type II integral membrane zinc-dependent metalloprotease in the M1 family of ectoenzymes (43), widely expressed on all myeloid cells, activated endothelial cells and epithelium of the kidney and intestine (44). Evolving evidence supported a role for ANPEP in controlling arterial blood pressure and the pathogenesis of hypertension by inhibiting renal tubule Na flux and modulating salt-adaptation (43,45). Interestingly, circulating ANPEP was found to be up-regulated in patients with essential hypertension and in the angiogenic vessels in the infarct area and border zone after myocardial infarction (44,46).…”

The Level and Significance of Circulating Angiotensin-III in Patients with Coronary Atherosclerosis

“…(2) We have known that Ang-III is mainly derived from the metabolism of Ang-II by APA and will be metabolized into Ang-IV by APN. In the peripheral circulation of patients with essential hypertension [22], APA activity is attenuated and APN activity is enhanced, presumably leading to decreased Ang-III production and increased metabolism. We get inspiration from this research, so we measured the concentration of APA in both groups.…”