title: Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin.
abstract: 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.
authors.affiliation: Department of In Vitro Sciences, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada. dave_percival@merck.com
authors.forename: M David
authors.initials: MD
authors.lastname: Percival
authors.forename: Sylvie
authors.initials: S
authors.lastname: Toulmond
authors.forename: Nathalie
authors.initials: N
authors.lastname: Coulombe
authors.forename: Wanda
authors.initials: W
authors.lastname: Cromlish
authors.forename: Sylvie
authors.initials: S
authors.lastname: Desmarais
authors.forename: Susana
authors.initials: S
authors.lastname: Liu
authors.forename: René
authors.initials: R
authors.lastname: St-Jacques
authors.forename: Jacques Yves
authors.initials: JY
authors.lastname: Gauthier
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Fournier
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D002401:Cathepsin B; D012083:Renin