Role of tissue kallikrein in response to flow in mouse resistance arteries.
BACKGROUND
Tissue kallikrein, an essential enzyme in the formation of vascular kinins, contributes to flow-dependent dilatation (FDD) in large arteries. We hypothesized that the vascular kinin-kallikrein system may be involved in shear stress signalling in small resistance arteries, which have a key role in the systemic regulation of blood pressure.


OBJECTIVE
To investigate the role of the vascular kallikrein-kinin system in mesenteric resistance arteries of mice during acute changes in blood flow.


METHODS
Arteries from wild-type mice (TK) and mice lacking tissue kallikrein (TK) were mounted in an arteriograph for the recording of changes in outer diameter during step increases in flow rate.


RESULTS
Responses to phenylephrine, acetylcholine or sodium nitroprusside were not different between the two strains. FDD was significantly reduced in arteries of TK mice compared with that in mesenteric arteries of TK mice exposed to phenylephrine (P = 0.04). FDD was no longer different between TK and TK mice when experiments were performed in the presence of the nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (l-NAME; P = 0.26), l-NAME plus diclofenac (P = 0.73), or l-NAME plus diclofenac plus potassium chloride (P = 0.31), indicating that inactivation of tissue kallikrein preferentially affects the contribution of nitric oxide to flow response. However, expression of endothelial NOS was comparable between TK and TK mesenteric arteries. Finally, the bradykinin B2 receptor antagonist, HOE-140, significantly decreased FDD in TK but not in TK arteries (P = 0.03 and P = 0.82, respectively).


CONCLUSIONS
These results demonstrate the specific role of the tissue kallikrein in flow-induced dilatation, which is mediated by nitric oxide and bradykinin B2 receptor activation in resistance arteries.
Bergaya
Sonia
S
Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 541, Hôpital Lariboisière and Inserm Unit 367, 17 rue du Fer à Moulin, Paris, France.
Matrougui
Khalid
K
Meneton
Pierre
P
Henrion
Daniel
D
Boulanger
Chantal M
CM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D004008:Diclofenac / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D020840:Tissue Kallikreins / Q000235:genetics* / Q000378:metabolism; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004008:Diclofenac; D009599:Nitroprusside; D010656:Phenylephrine; D020840:Tissue Kallikreins; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester