Morphological and biochemical characterization of remodeling in aorta and vena cava of DOCA-salt hypertensive rats

Abstract

Arterial remodeling occurs in response to mechanical and neurohumoral stimuli. We hypothesized that veins, which are not exposed to higher pressures in hypertension, would demonstrate less active remodeling than arteries. We assessed remodeling with two standard measures of arterial remodeling: vessel morphometry and the expression/function of matrix metalloproteinases (MMPs). Thoracic aorta and vena cava from sham normotensive and DOCA-salt hypertensive rats (110 +/- 4 and 188 +/- 8 mmHg systolic blood pressure, respectively) were used. Wall thickness was increased in DOCA-salt vs. sham aorta (301 +/- 23 vs. 218 +/- 14 mum, P < 0.05), as was medial area, but neither measure was altered in the vena cava. The aorta and vena cava expressed the gelatinases MMP-2, MMP-9, transmembrane proteinase MT1-MMP, and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemically, MMP-2 localized to smooth muscle in the aorta and densely in endothelium/smooth muscle of the vena cava. Western and zymographic analyses verified that MMP-2 was active in all vessels and less active in the vena cava than aorta. In hypertension, MMP-2 expression and activity in the aorta were increased (59.1 +/- 3.7 and 74.5 +/- 6.1 units in sham and DOCA, respectively, P < 0.05); similar elevations were not observed in the vena cava. MMP-9 was weakly expressed in all vessels. MT1-MMP was expressed by the aorta and vena cava and elevated in the vena cava from DOCA-salt rats. TIMP-2 expression was significantly increased in the aorta of DOCA rats compared with sham but was barely detectable in the vena cava of sham or DOCA-salt hypertensive rats. These findings suggest that large veins may not undergo vascular remodeling in DOCA-salt hypertension.

Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls

“…Rats were euthanized by an intraperitoneal injection of 60 -80 mg/kg pentobarbital; the thoracic aorta and vena cava were removed by dissection for each of the following protocols. Rat systolic blood pressures were measured by standard tail-cuff techniques, as previously described (20).…”

“…Bright-field IHC. IHC was performed as previously described (20). After being harvested and cleaned, the rat thoracic aorta and vena cava were formalin fixed, paraffin embedded, and sectioned (8 m).…”

“…Protein isolation, protein concentration determination, and Western blot analysis were performed as previously described (20). Briefly, 50 g of homogenized total protein from rat aorta and vena cava or smooth muscle cells cultured from these vessels were separated by gel electrophoresis, blotted onto a polyvinylidene difluoride membrane (TG1) or a nitrocellulose membrane (TG2), blocked for 3 h at 4°C in 4% (wt/vol) chick egg ovalbumin, and incubated overnight in primary antibody [mouse anti-TG1 (1:100, catalog no.…”

“…The aorta is composed of seven layers of smooth muscle, is a conduit vessel, and undergoes extensive remodeling, whereas the vena cava is composed of one layer of smooth muscle, is a capacitance vessel, and undergoes very little remodeling in response to hypertension, at least in DOCA-salt hypertension (20). In this way, the vena cava served as a comparison vessel because it is of similar size and proximity to the aorta.…”

Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance

“…The increased platelet count is also evidence of chronic inflammation [39]. can be further thickened under the action of other chemical or biological agents [46,47]. Thus, we did not expect prominent thickening of the aorta in the developed model of obese IR rats.…”