TY - JOUR
T1 - Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone
AU - Roksnoer, Lodi C. W.
AU - van Veghel, Richard
AU - Clahsen-van Groningen, Marian C.
AU - de Vries, Rene
AU - Garrelds, Ingrid M.
AU - Bhaggoe, Usha M.
AU - van Gool, Jeanette M. G.
AU - Friesema, Edith C. H.
AU - Leijten, Frank P. J.
AU - Hoorn, Ewout J.
AU - Danser, A. H. Jan
AU - Batenburg, Wendy W.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - ARNI [dual AT(1) (angiotensin II type 1) receptor-neprilysin inhibition] exerts beneficial effects on blood pressure and kidney function in heart failure, compared with ARB (AT(1) receptor blockade) alone. We hypothesized that ARNI improves cardiac and kidney parameters in diabetic TGR(mREN2) 27 rats, an angiotensin II-dependent hypertension model. Rats were made diabetic with streptozotocin for 5 or 12 weeks. In the final 3 weeks, rats were treated with vehicle, irbesartan (ARB) or irbesartan+thiorphan (ARNI). Blood pressure, measured by telemetry in the 5-week group, was lowered identically by ARB and ARNI. The heart weight/tibia length ratio in 12-week diabetic animals was lower after ARNI compared with after ARB. Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards. ARNI reduced proteinuria more strongly than ARB, and a similar trend was seen for albuminuria. Kidneys of ARNI-treated animals showed less severe segmental glomerulosclerosis than those of ARB-treated animals. After 12 weeks, no differences between ARNI-and ARB-treated animals were found regarding diuresis, natriuresis, plasma endothelin-1, vascular reactivity (acetylcholine response) or kidney sodium transporters. Only ARNI-treated rats displayed endothelin type B receptor-mediated vasodilation. In conclusion, ARNI reduces proteinuria, glomerulosclerosis and heart weight in diabetic TGR(mREN2) 27 rats more strongly than does ARB, and this occurs independently of blood pressure.
AB - ARNI [dual AT(1) (angiotensin II type 1) receptor-neprilysin inhibition] exerts beneficial effects on blood pressure and kidney function in heart failure, compared with ARB (AT(1) receptor blockade) alone. We hypothesized that ARNI improves cardiac and kidney parameters in diabetic TGR(mREN2) 27 rats, an angiotensin II-dependent hypertension model. Rats were made diabetic with streptozotocin for 5 or 12 weeks. In the final 3 weeks, rats were treated with vehicle, irbesartan (ARB) or irbesartan+thiorphan (ARNI). Blood pressure, measured by telemetry in the 5-week group, was lowered identically by ARB and ARNI. The heart weight/tibia length ratio in 12-week diabetic animals was lower after ARNI compared with after ARB. Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards. ARNI reduced proteinuria more strongly than ARB, and a similar trend was seen for albuminuria. Kidneys of ARNI-treated animals showed less severe segmental glomerulosclerosis than those of ARB-treated animals. After 12 weeks, no differences between ARNI-and ARB-treated animals were found regarding diuresis, natriuresis, plasma endothelin-1, vascular reactivity (acetylcholine response) or kidney sodium transporters. Only ARNI-treated rats displayed endothelin type B receptor-mediated vasodilation. In conclusion, ARNI reduces proteinuria, glomerulosclerosis and heart weight in diabetic TGR(mREN2) 27 rats more strongly than does ARB, and this occurs independently of blood pressure.
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=eur_pure&SrcAuth=WosAPI&KeyUT=WOS:000393761000007&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1042/CS20160197
DO - 10.1042/CS20160197
M3 - Article
C2 - 27129187
SN - 0143-5221
VL - 130
SP - 1209
EP - 1220
JO - Clinical Science
JF - Clinical Science
IS - 14
ER -
