Vascular Reactivity in Old Spontaneously Hypertensive Stroke-Prone Rats: Effects of Prolonged Ischemia followed by Reperfusion

Objectives: Peripheral arterial disease, which comprises atherosclerosis of the aorta and lower extremities, commonly results in tissue ischemia. Medical intervention strategies to restore blood flow can induce reperfusion injury. Hypertension and older age are both risk factors for vascular disorders. We investigated the effects of hypertension and aging on vascular graft responsiveness under normoxia and ischemia/reperfusion (IR) conditions.

Methods: Hemodynamic changes and histological aortic morphometry were studied in 18-month-old spontaneously hypertensive stroke prone (SHRSP, n = 8) and age-matched normotensive Wistar (control, n = 8) rats. Although 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 24 hours of cold ischemic preservation.

Result: Significantly increased intima-media thickness, intima-media cross-sectional area, and lumen normalized to body weight were observed in SHRSP rats displaying a systolic blood pressure of 205 ± 16 mm Hg compared with controls 124 ± 8 mm Hg, p < 0.05. Even though aortic rings from the SHRSP rats showed significantly greater maximum contraction to phenylephrine compared with controls, the SHRSP-IR group had impaired contraction (control 2.2 ± 0.1 g vs. SHRSP 2.9 ± 0.1 g vs. control-IR 2.5 ± 0.1 g vs. SHRSP-IR 0.9 ± 0.1 g, p < 0.05). In contrast to phenylephrine, vasoconstrictive response to high K+-induced depolarization was significantly reduced in SHRSP-, control-IR-, and SHRSP-IR groups compared with controls. Additionally, high K+–induced contraction was significantly reduced in SHRSP-IR group compared with control-IR group (control 4.7 ± 0.1 g vs. SHRSP 3.4 ± 0.1 g vs. control-IR 2.5 ± 0.1 g vs. SHRSP-IR 0.7 ± 0.1 g, p < 0.05). IR significantly reduced maximum endothelium-dependent relaxation to acetylcholine in the control group, whereas unexpectedly, it had no effect in SHRSP rats (control 57.0 ± 2.0% vs. SHRSP 49.6 ± 2.2% vs. control-IR 44.1 ± 2.7% vs. SHRSP-IR 48.2 ± 2.9%, p < 0.05). While IR had no effect on hypoxia-inducible factor-1α protein expression in the control rats, its expression was significantly decreased in the SHRSP-IR group compared with the SHRSP.

Conclusion: IR impairs vascular smooth muscle contractility in response to α1-adrenergic stimulation and to high K+-induced depolarization in 18-month-old hypertensive rats, whereas it has no impact on endothelial function.

Publication History

Article published online:
19 February 2021