Vascular Smooth Muscle Reactivity in Old Spontaneously Hypertensive Stroke-Prone Rats: Effects of Prolonged Cold Ischemia Followed by Warm Reperfusion in an In Vitro Model

Objectives: Vascular grafts are essential therapeutic materials for bypass surgery. However, age and arterial hypertension are risk factors for cardiovascular complications after artery bypass graft surgery. We investigated the effects of both hypertension and aging on vascular graft responsiveness in normoxic and prolonged cold ischemia/warm reperfusion (IR) conditions.

Methods: In 18-month-old spontaneously hypertensive stroke-prone (shrsp, n = 7) and age-matched normotensive Wistar (n = 8) rats systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) values were recorded. Whereas thoracic aortic rings in the control and shrsp groups were immediately mounted in an organ bath (normoxia group), aortic segments in the control-IR and shrsp-IR groups underwent 24h cold ischemic preservation in physiological saline, followed by reperfusion injury simulated by hypochlorite exposure. Changes in isometric force were recorded.

Results: SBP, DBP, and MAP were significantly higher in shrsp than in control (control SBP 134 ± 7; DBP 108 ± 6; MAP 117 ± 6 vs. shrsp SBP 201 ± 18; DBP 162 ± 10; MAP 175 ± 13mmHg). Even though aortic rings from shrsp group showed significantly greater maximal contraction to phenylephrine an α1-adrenergic agonist compared with control, shrsp-IR group showed further impaired contraction (control 2.2 ± 0.1 vs. shrsp 2.9 ± 0.1 vs. control-IR 2.6 ± 0.2 vs. shrsp-IR 0.9 ± 0.1 g). In contrast to phenylephrine, all groups showed significantly reduced vasoconstriction responses to high K⁺-induced depolarization when compared with control. Additionally, both IR-groups showed significantly weaker tension compared with shrsp-group, and IR in shrsp rat further impaired high K⁺-induced contraction (control 4.7 ± 0.1 vs. shrsp 3.6 ± 0.1 vs. control-IR 2.6 ± 0.2 vs. shrsp-IR 0.7 ± 0.1 g). Maximal endothelium-dependent relaxation to acetylcholine was significantly weaker in rings from both IR-groups compared with control-group (control 57 ± 2 vs. shrsp 48 ± 3 vs. control-IR 44 ± 3 vs. shrsp-IR 44 ± 3%), and IR significantly decreased the sensitivity of aortic rings to acetylcholine in shrsp rats compared with normoxia shrsp-group. Maximal endothelium-independent relaxation to sodium nitroprusside was not significantly impaired in both IR-groups compared with control.

Conclusion: Cold ischemia/warm reperfusion, in senescent shrsp rats with established hypertension, increases the susceptibility of aortic rings to smooth muscle contraction impairment.