Pretreatment with the ACE inhibitor lisinopril prevented the pressor response to ANG-(1-12) and suppressed ANG II formation in both normotensive and hypertensive rats, whereas chymase inhibition had no effect.
Does ACE or chymase inhibition alter angiotensin peptide formation during ANG-(1-12) infusion in WKY and SHR rats?
ACE acts as the primary enzyme for the conversion of ANG-(1-12) to smaller angiotensin peptides in the circulation of WKY and SHR rats.
Angiotensin-(1-12) ANG-(1-12), a new member of the renin-angiotensin system, is recognized as a renin independent precursor for ANG II. However, the processing of ANG-(1-12) in the circulation in vivo is not fully established. We examined the effect of angiotensin converting enzyme (ACE) and chymase inhibition on angiotensin peptides formation during an intravenous infusion of ANG-(1-12) in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR were assigned to a short ANG-(1-12) infusion lasting 5, 15, 30, or 60 min (n = 4-10 each group). In another experiment WKY and SHR were assigned to a continuous 15-min ANG-(1-12) infusion with pretreatment of saline, lisinopril (10 mg/kg), or chymostatin (10 mg/kg) (n = 7-13 each group). Saline or lisinopril were infused intravenously 15 min before the administration of ANG-(1-12) (2 nmol·kg(-1)·min(-1)), whereas chymostatin was given by bolus intraperitoneal injection 30 min before ANG-(1-12). Infusion of ANG-(1-12) increased arterial pressure and plasma ANG-(1-12), ANG I, ANG II, and ANG-(1-7) levels in WKY and SHR. Pretreatment with lisinopril caused increase in ANG-(1-12) and ANG I and large decreases in ANG II compared with the other two groups in both strains. Pretreatment of chymostatin had no effect on ANG-(1-12), ANG I, and ANG II levels in both strains, whereas it increased ANG-(1-7) levels in WKY. We conclude that ACE acts as the primary enzyme for the conversion of ANG-(1-12) to smaller angiotensin peptides in the circulation of WKY and SHR and that chymase may be an ANG-(1-7) degrading enzyme.
Moniwa et al. (Sat,) conducted a other in Hypertension (n=91). Lisinopril or Chymostatin vs. Saline was evaluated on Plasma angiotensin peptide concentrations and mean arterial pressure response to ANG-(1-12) infusion. Pretreatment with the ACE inhibitor lisinopril prevented the pressor response to ANG-(1-12) and suppressed ANG II formation in both normotensive and hypertensive rats, whereas chymase inhibition had no effect.
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