Relationship Between Elastin Organisation and Structural and Mechanical Abnormalities in Resistance Arteries From Spontaneously Hypertensive Rats

Briones, A., González, J. M., Somoza, B., Giraldo, J., Daly, C. , McGrath, I. , Vila, E., González, C. and Arribas, S. M. (2003) Relationship Between Elastin Organisation and Structural and Mechanical Abnormalities in Resistance Arteries From Spontaneously Hypertensive Rats. XXXII Congress of the Spanish Society of Physiological Sciences International Joint Meeting with The Physiological Society, Puerto de la Cruz, Tenerife, 13-17 Feb 2003.

Abstract

Hypertension is associated with alterations in vascular structure and mechanics. In resistance arteries these modifications have been mainly attributed to changes in collagen. Elastin, an important determinant of vascular elasticity, has been less studied. The aim of the present work has been to study the role of elastin in the structural and mechanical abnormalities in resistance arteries from hypertensive rats. Structural and mechanical characteristics of mesenteric resistance (MRA) and middle cerebral (MCA) arteries from adult spontaneously hypertensive (SHR, n = 10) and normotensive Wistar Kyoto rats (WKY, n = 7) were studied with pressure myography. Rats were killed with 50 mg kg-1 pentobarbital I.P. following EU guidelines. Briefly, arterial segments were pressurised at a range of pressures (10-120 mm Hg) in 20 mmHg steps and internal and external diameters were measured in active (physiological salt solution, PSS) and passive (0 calcium PSS) conditions. From these measurements incremental distensibility-pressure and stress-strain curves were calculated to determine arterial distensibility and elasticity, respectively. Thereafter, arteries were pressure-fixed at 70 mmHg in 4 % paraformaldehyde and elastin content and 3-D structure was analysed with fluorescent confocal microscopy (Leica TCS SP2) and image analysis software (Metamorph) using the autofluorescent properties of elastin (Ex 488 nm/Em 515 nm). When compared to WKY rats, MRAs from SHR showed: (i) a significantly smaller lumen diameter in active (at 60 mmHg: WKY = 295 ± 15; SHR = 250 ± 11µm, P < 0.05, 2-way ANOVA) and passive conditions (at 60 mmHg: WKY = 313 ± 8; SHR = 260 ± 7 µm, P < 0.05, 2-way ANOVA). This was observed at all pressures tested; (ii) significantly decreased distensibility at low pressures (at 20 mmHg: WKY = 1.46 ± 0.06; SHR = 1.00 ± 0.04 % mmHg-1, P < 0.01, 2-way ANOVA); (iii) a leftward shift of the stress-strain curve with a significantly increased β value (WKY = 3.9 ± 0.1; SHR = 4.5 ± 0.2; P < 0.05, Student’s unpaired t test). MCAs from SHR showed a significant reduction of lumen in active (at 60 mmHg: WKY = 206 ± 9; SHR = 171 ± 18 µm, P < 0.05, 2-way ANOVA), but not in passive conditions (at 60 mmHg: WKY = 236 ± 7; SHR = 230 ± 8 µm, n.s., 2-way ANOVA), and no difference in the mechanical parameters studied (β value: WKY = 4.7 ± 0.4; SHR = 5.5 ± 0.6, n.s., Student’s unpaired t test). With respect to elastin organisation, MRA showed a a network of elastin fibres in the adventitia and a well defined internal elastic lamina (IEL). In MRAs from SHR, 3-D structure of IEL was altered, with a significant increase in the relative area occupied by elastin (SHR = 0.83 ± 0.02; WKY = 0.5 ± 0.04; Student’s unpaired t test, P < 0.01) and smaller fenestra. However, total elastin content was similar between strains due to the reduced luminal surface area of SHR MRAs (SHR = 0.76 ± 0.02 mm2; WKY = 0.91 ± 0.05 mm2; P < 0.05). Elastin distribution in the adventitia was not different between strains. In MCA only a thin IEL was visible and elastin content and structure was similar between strains. In conclusions, (1) the inward remodelling observed in MRAs from SHR is accompanied by a re-organisation of elastin in the IEL. This alteration can be responsible for the reduced elasticity observed at low pressures. (2) MCAs from SHR did not show alterations in structure, mechanics or elastin organisation. The reduction in MCA internal diameter in active conditions is due to an increase in the intrinsic tone of the artery. This work was supported by the EC RTD (contract QLG1-CT-1999-00084 ‘VASCAN-2000′).

• Item Type: Conference or Workshop Item
• Additional Information: Oral Communication.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGrath, Professor John and Daly, Professor Craig and Briones, Dr Ana
• Authors: Briones, A., González, J. M., Somoza, B., Giraldo, J., Daly, C., McGrath, I., Vila, E., González, C., and Arribas, S. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences