Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin.
During pregnancy and chronic relaxin administration to nonpregnant rats (for days), vascular MMP (matrix metalloproteinase)-2 is increased and mediates renal vasodilation, hyperfiltration, and inhibition of myogenic reactivity of small renal arteries. However, the renal vasodilatory actions of relaxin also occur after only several hours of hormone administration to nonpregnant rats, and we hypothesized a pivotal role for vascular MMP-2. Accordingly, we used gelatin zymography, which reveals not only vascular MMP-2, but also MMP-9 activity in small renal arteries isolated from rats administered recombinant human relaxin (rhRLX) or vehicle for 4-6 h. Furthermore, we tested whether myogenic reactivity is inhibited, and if so, whether the inhibition is mediated by increased vascular MMP-2. Surprisingly, we detected no significant difference in either pro or active MMP-2 in small renal arteries isolated from rhRLX and vehicle control treatment groups. In contrast, vascular MMP-9 was up-regulated by 70% (P < 0.0005 vs. vehicle). These results were completely unexpected and novel. MMP-9 protein expression was confined to the vascular smooth muscle. MMP-9, but not MMP-2 activity, was also increased in mesenteric arteries after short-term rhRLX administration (P < 0.005 and >0.05 vs. vehicle, respectively). Myogenic reactivity was inhibited in small renal arteries isolated from nonpregnant rats treated with rhRLX for 4-6 h (P < 0.01 vs. vehicle) and was completely restored by incubation with MMP-9, but not MMP-2 neutralizing antibodies in vitro.


CONCLUSIONS
In contrast to chronic rhRLX administration, MMP-9 rather than MMP-2 plays a central role in the vasodilatory effect of short-term relaxin administration.
Jeyabalan
Arundhathi
A
Department of Obstetrics, Gynecology and Reproduction Sciences, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Novak
Jacqueline
J
Doty
Ketah D
KD
Matthews
Julianna
J
Fisher
Michelle C
MC
Kerchner
Laurie J
LJ
Conrad
Kirk P
KP
D000818:Animals; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D011994:Recombinant Proteins / Q000494:pharmacology; D012065:Relaxin / Q000494:pharmacology*; D012077:Renal Artery / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D011994:Recombinant Proteins; D012065:Relaxin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9