Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase ( eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide ( NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral ( U) or bilateral ( B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor ( EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance ( RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 mu M furosemide. Autoregulation was enhanced by N-omega-nitro-L-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

Voices of lay principals: Promoting a Catholic character and culture in schools in an era of change

This paper reports a qualitative study of the practice of leadership in Catholic schools to ascertain the perceptions of lay principals, who as positional leaders play a critical role in embracing and creatively rebuilding the Catholic vision of life within the reality that the Catholic school principalship is now a ministry of the laity. The methodology included semi-structured interviews, field notes, reflexive journals, direct observation, and document nalysis. The study examined both individual human behaviour and the structure of the social order in Catholic schools. The findings point towards successful leadership in Catholic schools being highly influenced by the cultural and spiritual capital that a principal brings to a school signifying a fundamental importance of appointing principals who are not only professionally competent but spiritually as well. In an era of unprecedented social, educational and ecclesial change, and with an ever widening role description, lay principals are challenged to redefine and re-articulate their Catholic character and identity, and will need to look for new ways to make this explicit. Embracing a new leadership paradigm of shared leadership, the preparation and on-going formation of lay principals were identified as critical for the continuance of the Catholic school’s distinctive mission in the future.