Question

Individuals with diabetes mellitus have an increased risk for developing kidney disease due to accumulated damage to the nephrons. Based on our discussion of filtration, explain how an ACE inhibitor may prevent damage to the kidney individuals with diabetes. Explain how an ACE inhibitor works, what blood vessel(s) and any other structures that would be directly impacted by an ACE inhibitor, and how treatment with an ACE inhibitor could prevent damage to the nephrons.

Answer 1

Ans:-

MECHANISM OF ACE INHIBITORS:-ACE inhibitor s abolishes the pressor action of Ang I but not that of Ang II: does not block AT1 or AT2 receptors. ACE is a relatively nonspecific enzyme; splits off a dipeptidyl segment from several peptides including bradykinin, substance P, , etc. in addition to Ang I. As such, captopril increases plasma kinin levels and potentiates the hypotensive action of exogenously administered bradykinin. Pretreatment with B2 kinin receptor antagonist has shown that kinins do contribute to the acute vasodepressor action of ACE inhibitors, but they appear to have little role in the long-term hypotensive effect, probably because, firstly kinins play only a minor role, if at all, in BP regulation, and, secondly another enzyme ‘Kininase I’ (which also degrades bradykinin) is not inhibited by captopril. ACE inhibitors interfere with degradation of substance P also. It responsible for their cardioprotective effect in CHF.

• Treatment with ACE inhibitors causes feedback increase in renin release resulting in overproduction of Ang I. Since its conversion to Ang II is blocked, Ang I is diverted to produce more Ang (1-7) which has vasodilator property, and could contribute to the BP lowering action of ACE inhibitors.
• ACE inhibitor effect on kidney in dibetes nephropathy:-Prolonged ACE inhibitor therapy has been found to prevent or delay end-stage renal disease in type I as well as type II diabetics. Albuminuria (an index of glomerulopathy) remains stable in those treated with ACE inhibitor, but aggravates in untreated diabetics. Treated patients have higher creatinine clearance, require less dialysis and have longer life expectancy. Benefits appear to be due to haemodynamic (systemic and intrarenal) as well as abnormal mesangial cell growth attenuating effects of ACE inhibitors.