Abstract P243: Smooth Muscle Cullin-3 Deficiency Causes Severe Early Onset Hypertension and Nitric Oxide Resistance
| Autor: | Larry N Agbor, Anand Nair, Jing Wu, Deborah R Davis, Henry L Keen, Frederick W Quelle, James A McCormick, Jeffrey D Singer, Curt D Sigmund |
|---|---|
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Hypertension. 70 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Mutations in Cullin-3 ( Cul3 ) resulting in exon 9 skipping (CUL3α9) cause human hypertension. We demonstrated that selective expression of CUL3α9 in smooth muscle causes arterial stiffness and hypertension. We hypothesized that deletion of CUL3 in smooth muscle causes severe hypertension. Mice carrying a conditional allele of CUL3 were bred with mice expressing a tamoxifen-inducible CRE-recombinase driven by a smooth muscle promoter. Mice were administered tamoxifen i.p. (75 mg/kg) for 5 consecutive days to generate smooth muscle CUL3 knockout (S-CUL3KO). CUL3 protein was undetectable whereas Cullin-1 protein was preserved in aorta from S-CUL3KO mice. We assessed vascular function in the cerebral basilar artery and aorta using pressurized and wire myograph, respectively. Blood pressure (BP) was measured by radiotelemetry. S-CUL3KO mice exhibited significantly increased systolic BP (SBP) at 2 weeks and 4 weeks post tamoxifen compared to corn oil controls (2 wks SBP mmHg: 145±1 vs 115±2, p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|