Vascular reactivity in old spontaneously hypertensive stroke-prone rats- effects of in vitro ischemia/reperfusion injury

Objectives: Peripheral arterial disease affects mainly the aorta and lower extremities and commonly results in tissue ischemia. Medical interventions to restore blood flow can induce reperfusion injury. We investigated the effects of both hypertension and ageing on vascular graft responsiveness under normoxia and ischemia/reperfusion (IR) conditions. Methods: Hemodynamic changes and aortic morphometry were studied in 18-month-old spontaneously hypertensive stroke prone (SHRSP, n=8) and age-matched normotensive Wistar (control, n=8) rats. Whereas thoracic aortic rings of the control- and SHRSP groups were immediately mounted in organ bath chambers (normoxia-group), aortic segments in the control-IR and SHRSP-IR groups underwent cold ischemic preservation, prior to mounting. Results: Significantly increased intima-media thickness, intima-media cross-sectional area, and lumen normalized to body weight were observed in SHRSP displaying a systolic blood pressure of 205±16 mmHg compared to controls 124±8 mmHg, p < 0.05. Phenylephrine-induced vasoconstriction was greater in aorta of SHRSP compared to controls. IR injury increased contractile responses to phenylephrine in both control and SHRSP compared to the corresponding groups, which was further increased in SHRSP-IR compared to control-IR (as percentage of KCl-contraction: SHRSP-IR 167±26% vs. control-IR 101±5%, p < 0.05). Compared to controls, vasoconstrictive response to high K+-induced depolarization was significantly reduced in SHRSP, control-IR, and SHRSP-IR. Additionally, KCl-induced contraction was reduced in SHRSP-IR compared to control-IR (SHRSP-IR 0.7±0.1g vs. control-IR 2.5±0.1g, p < 0.05). IR reduced maximum endothelium-dependent relaxation to acetylcholine in the normoxia control group, whereas it had no effect in the aortic rings from SHRSP. Conclusions: IR increases the susceptibility of aortic rings to vascular smooth muscle contractile dysfunction in 18-month-old hypertensive rats.