L-arginase induces vascular dysfunction in old spontaneously hypertensive rats

  • O Arishe
  • J McKenzie
  • F Priviero
  • A.B. Ebeigbe
  • R Clinton Webb
Keywords: Hypertension, Arginase, aging, vascular dysfunction, endothelium, Nitric oxide

Abstract

Background: Aging is a major non-modifiable risk factor for hypertension. Changes in aging are similar to those seen in hypertension in the vasculature. Also, aging increases the vascular dysfunction that occurs in hypertension. L-arginase action reduces substrate (L-arginine) availability for the formation of nitric oxide (NO). This reduces the level of NO and leads to reduced vasodilation and ultimately, vascular dysfunction. This study examines the hypothesis that age-dependent vascular dysfunction in SHRs is mediated by arginase.

Methods: Young (12-14 weeks) and old (11-12 months) male Wistar and spontaneously hypertensive rats (SHR) were used. Mean arterial pressure (MAP) was measured in the rats. They were then euthanized and mesenteric resistance arteries (MRAs) and thoracic aortae were excised and placed in ice-cold physiological salt solution (PSS). Arterial segments were either snap-frozen in liquid nitrogen and stored for immunoblotting studies or cut into 2mm rings for reactivity studies. Cumulative concentration-response curves to acetylcholine (Ach; 10-9 – 3x10-5M) and sodium nitroprusside (SNP; 10-12 – 3x10-5 M) were performed in the absence or presence (30-minute exposure) of L-arginase, 0.05U/ML (MRA) or 0.5U/ML (aorta). Vessels were pre-contracted with phenylephrine (PE; 3x10-6M)

Results: MAP increased during aging in the SHRs p<0.05 but not in the Wistar rats. Arginase impaired the endothelium-dependent relaxation responses of thoracic aortic and MRA arterial rings to Ach in the old Wistars and SHRs (Emax aorta: 29.42±2.19% vs 7.94±1.86%). Arginase also impaired endothelium-independent relaxation response to SNP in the old SHRs only (Emax aorta: 88.62±4.10% vs 31.45±10.61%). We also observed no differences in the serum arginase activity in the four groups of rats. On the contrary, arginase activity in the aortae of young Wistar rats was reduced compared to other groups.

Conclusions: Arginase impairs both endothelium-dependent and –independent vasorelaxation responses, through the NO signaling pathway.

Keywords: Hypertension, Arginase, aging, vascular dysfunction, endothelium, Nitric oxide

Published
2020-01-30
Section
Articles

Journal Identifiers


eISSN: 2449-108X
print ISSN: 2315-9987