Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin

Arundhathi Jeyabalan, Jacqueline Novak, Ketah D. Doty, Julianna Matthews, Michelle Freeman, Laurie J. Kerchner, Kirk P. Conrad

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Abstract

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalEndocrinology
Volume148
Issue number1
DOIs
StatePublished - Jan 5 2007

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Relaxin
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Blood Vessels
Arteries
Renal Artery
Kidney
Gelatin
Neutralizing Antibodies
Vasodilation
Hormones
Pregnancy
Control Groups

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Jeyabalan, Arundhathi ; Novak, Jacqueline ; Doty, Ketah D. ; Matthews, Julianna ; Freeman, Michelle ; Kerchner, Laurie J. ; Conrad, Kirk P. / Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin. In: Endocrinology. 2007 ; Vol. 148, No. 1. pp. 189-197.
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abstract = "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. Conclusion: 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.",
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Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin. / Jeyabalan, Arundhathi; Novak, Jacqueline; Doty, Ketah D.; Matthews, Julianna; Freeman, Michelle; Kerchner, Laurie J.; Conrad, Kirk P.

In: Endocrinology, Vol. 148, No. 1, 05.01.2007, p. 189-197.

Research output: Contribution to journalArticle

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T1 - Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin

AU - Jeyabalan, Arundhathi

AU - Novak, Jacqueline

AU - Doty, Ketah D.

AU - Matthews, Julianna

AU - Freeman, Michelle

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AU - Conrad, Kirk P.

PY - 2007/1/5

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N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

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