Abstract
In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamyl-aminopeptidase activities were determined fluorometrically using aminoacyl-β-naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.
Highlights
The study of the renin-angiotensin system (RAS) remains one of the main objectives to better understand the pathogenesis of hypertension as well as to obtain suggestions for its treatment [1,2,3,4]
In the present study, we analyzed the activity of several aminopeptidases involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME)
Focusing on the steps of the enzymatic cascade where the enzymes analyzed in this work act (Figure 1), Ang II is metabolized to Ang III by glutamate aminopeptidase (EC 3.4.11.7, GluAP) and Ang III is further metabolized to Ang IV by the action of alanine aminopeptidase (EC 3.4.11.2, AlaAP) [5]
Summary
The study of the renin-angiotensin system (RAS) remains one of the main objectives to better understand the pathogenesis of hypertension as well as to obtain suggestions for its treatment [1,2,3,4]. Ang IV can bind to the AT4 receptor, which has been described to be identical to insulin-regulated aminopeptidase (IRAP) or vasopressinase, whose activity can be measured as cystine aminopeptidase (EC 3.4.11.3, CysAP) [6,7]. The stimulatory action of Ang III on the posterior pituitary for vasopressin secretion has been described o[9f ]1.3 Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) are strains frequently used to study the role of RAS in hypertension as well as in its treatment [10,11]
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