Effects of chymostatin, a chymase inhibitor, on blood pressure, plasma and tissue angiotensinII, renal haemodynamics and renal excretion in two models of hypertension in the rat
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Experimental Physiology
ISSN
0958-0670
EISSN
1469-445X
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2015
Numer zeszytu
9
Strony od-do
1093-1105
Numer tomu
100
Identyfikator DOI
Liczba arkuszy
1,40
Słowa kluczowe
en
DAHL-S RATS
II-GENERATING ENZYMES
CONVERTING ENZYME
VASCULAR CHYMASE
FORMING ENZYME
HEART-FAILURE
PREVENTION
ELASTASE-2
KIDNEY
ACE
Streszczenia
Język
en
Treść
New Findings What is the central question of this study? We examined, in hypertensive rats, whether the angiotensin-converting enzyme-independent enzymes generating angiotensinII in the tissues modulate blood pressure, peripheral circulation and renal function. What is the main finding and its importance? The results suggest that chymostatin-sensitive enzymes diminish vascular tone in renal and extrarenal vascular beds. Chymase or similar chymostatin-sensitive enzymes have a significant role in the synthesis of angiotensinII in different tissues but do not control blood pressure in the short term, similarly in salt-dependent or Goldblatt-type rat hypertension. In salt-dependent hypertension, chymase blockade protected renal outer medullary perfusion, probably by reducing the angiotensinII content in the kidney. Chymase is presumed to be a crucial enzyme of the non-angiotensin-converting enzyme pathway of angiotensinII (AngII) generation in tissues, a process involved in vascular remodelling and development of hypertension. We examined the role of chymase in hypertension induced by exposure of uninephrectomized rats to high dietary salt intake (UNX HS) and in the Goldblatt renal artery stenosis (two-kidney, one-clip) model. In acute experiments with anaesthetized rats of either model, chymostatin at 2mgkg(-1)h(-1) or 0.05\% DMSO solvent was infused i.v. Mean arterial blood pressure, heart rate, iliac blood flow (a measure of hindlimb perfusion), total renal blood flow and intrarenal regional perfusion (laser-Doppler technique) were measured continuously, along with the glomerular filtration rate and renal excretion. In both models, chymase blockade distinctly decreased plasma and tissue AngII without lowering mean blood pressure or consistently altering the other functional parameters measured. Unexpectedly, in Goldblatt hypertensive rats the blockade increased the renal and hindlimb vascular resistances by 51 and 33\%, respectively (P<0.05). In UNX HS hypertensive rats, chymase blockade abolished the solvent-induced decrease in outer medullary blood flow. We conclude that chymase or similar chymostatin-sensitive enzyme(s) has a significant role in the synthesis of AngII in different tissues but does not participate in short-term control of blood pressure in salt-dependent or Goldblatt-type rat hypertension. In the Goldblatt model, chymase appeared to reduce the renal and hindlimb vascular resistances by an unknown mechanism. In salt-dependent hypertension, chymase blockade protected renal outer medullary perfusion, probably by reducing AngII content in the kidney.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
660971
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