Abstract WP440: Relaxin Selectively Affects Brain Parenchymal Arteriolar Structure during Hypertension
Background: Cerebral small vessel disease (SVD) is a common hypertension-related vasculopathy of the penetrating arterioles (PA) that causes lacunar stroke, white matter lesions and vascular dementia. We investigated the effect of chronic hypertension on PA structure and if treatment with relaxin, a hormone with cardioprotective effects previously shown to promote selective outward remodeling of PA in normotensive animals, could reverse these effects.
Methods: Female SHR rats (n=7-8/group) were treated in vivo with relaxin (4μg/hr) or vehicle for 2 weeks and studied at 18 weeks of age. Aged-matched WKY rats were used as controls. Middle cerebral arteries (MCA) and PA from the same animals were isolated and studied under pressurized conditions in zero calcium buffer to obtain structural measurements. Blood pressures were measured using tail cuff after 3 days of training.
Results: PA inner and outer diameters were smaller in SHR vs. WKY: at 100 mmHg PA inner and outer diameters were 59 ± 3 and 72 ± 3 μm for WKY vs. 50 ± 3 and 63 ± 3 μm for SHR (p<0.01). Relaxin treatment of SHR reversed this rarefaction such that inner and outer diameters were similar to WKY: 58 ± 4 and 69 ± 4 μm (p<0.01 vs. SHR; Figure). The increase in PA size with relaxin treatment was related to a large increase in distensibility (Figure). Percent distensibility of PA for WKY, SHR and SHR+relaxin was: 18 ± 3%, 13 ± 2% and 40 ± 4% (p<0.01). Relaxin treatment had no effect on MCA in SHR that were smaller than WKY: MCA inner and outer diameters were 258 ± 4 and 285 ± 5 μm in WKY, 228 ± 5 and 260 ± 5 μm in SHR and 225 ± 4 and 256 ± 4 μm in SHR+relaxin (p>0.05). Relaxin also did not lower blood pressures that were higher in SHR: MAP for WKY, SHR and SHR+relaxin was: 94 ± 3, 138 ± 2 and 144 ± 5 mmHg (p<0.01 vs. WKY).
Conclusion: These results suggest that relaxin may be an effective treatment for hypertension-induced rarefaction and increased stiffness of PA that underlies SVD in the brain.
- © 2012 by American Heart Association, Inc.