Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin.
Renin is the first enzyme in the renin-angiotensin-aldosterone system which is the principal regulator of blood pressure and hydroelectrolyte balance. Previous studies suggest that cathepsin B is the activator of the prorenin zymogen. Here, we show no difference in plasma renin activity, or mean arterial blood pressure between wild-type and cathepsin B knockout mice. To account for potential gene compensation, a potent, selective, reversible cathepsin B inhibitor was developed to determine the role of cathepsin B on prorenin processing in rats. Pharmacological inhibition of cathepsin B in spontaneously hypertensive and double transgenic rats did not result in a reduction in renal mature renin protein levels or plasma renin activity. We conclude that cathepsin B does not play a significant role in this process in rodents.
Percival
M David
MD
Department of In Vitro Sciences, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada. dave_percival@merck.com
Toulmond
Sylvie
S
Coulombe
Nathalie
N
Cromlish
Wanda
W
Desmarais
Sylvie
S
Liu
Susana
S
St-Jacques
René
R
Gauthier
Jacques Yves
JY
Fournier
Jean-Francois
JF
D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism*
D004791:Enzyme Inhibitors; D002401:Cathepsin B; D012083:Renin