SHR treated with a moderate dose of a NOS inhibitor), to study renal function and to characterise endothelial function. The purpose of the present work was, in the accelerated model of hypertension associated with kidney damage (i.e. In hypertension, this endothelial dysfunction is characterized by an alteration of the balance between endothelial vasoconstrictor and vasodilator responses ( Büssemaker et al., 2003 Félétou and Vanhoutte, 2006a Michel et al., 2008). In the renal vasculature, endothelium-dependent vasodilatation is an important regulatory mechanism and disruption of these processes, including the activity of various populations of potassium channels, can profoundly alter haemodynamic resistance, renal blood flow and, hence, affect glomerular filtration pressure and renal function ( Benter et al., 2005 Sorensen et al., 2012). In addition, they also elicit endothelium-dependent hyperpolarizations (EDHF-mediated responses Félétou et al., 2011). This experimental model of severe hypertension and nephrosclerosis is also associated with cardiac fibrosis and arterial stiffening ( Ono et al., 2001 Terata et al., 2003 Zhou and Frohlich, 2007 Vayssettes-Courchay et al., 2008 2011 Isabelle et al., 2012).Įndothelial cells control vascular tone not only by releasing NO but also by generating other vasoactive mediators such as metabolites of arachidonic acid.
However, SHR treated with a moderate dose of a NOS inhibitor show impaired kidney function and altered renal structures similar to those observed in untreated, ageing SHR, and hence, represents an accelerated model of hypertension associated with kidney damage ( Zhou and Frohlich, 2007). However, this interesting model is difficult to manage since SHR require careful husbandry and up to the age of 12–16 months when these renal dysfunctions become manifest ( Zhou and Frohlich, 2007). elevated renal vascular resistance, impaired renal functions and increased renal fibrosis). The aging spontaneously hypertensive rat (SHR) is an animal model exhibiting end-stage renal disease that shows some similarities with those observed in clinical hypertension (i.e. Hypertension is a major pathological factor in the development of cardiovascular disease and in the progression towards end-stage renal disease, the incidence of both being increased during aging ( Zhou and Frohlich, 2007).
Dilatation induced by an opener of K Ca3.1/K Ca2.3 channels, NS-309, was also blocked by TRAM-34, but not by apamin. However, the addition of TRAM-34 (or charybdotoxin) inhibitors of Ca 2+-activated K + channels of intermediate conductance (K Ca3.1), blocked the vasodilatation to acetylcholine, while apamin, an inhibitor of Ca 2+-activated K + channels of small conductance (K Ca2.3), was ineffective. Further addition of ODQ, an inhibitor of soluble guanylyl cyclase, abolished the responses to sodium nitroprusside but did not affect the vasodilatation to acetylcholine. In vitro administration of indomethacin did not alter the vasodilatation, while the addition of N w-nitro-L-arginine (L-NA) produced a differential inhibition of the vasodilatation, (inhibition in WKY > SHR > L-NAME-treated SHR). KEY RESULTS Acetylcholine caused similar dose-dependent renal dilatation in the three groups. BACKGROUND AND PURPOSE The purpose of the study was to investigate renal endothelium-dependent vasodilatation in a model of severe hypertension associated with kidney injury.ĮXPERIMENTAL APPROACH Changes in perfusion pressure were measured in isolated, perfused kidneys taken from 18-week-old Wistar–Kyoto rat (WKY), spontaneously hypertensive rats (SHR) and SHR treated for 2 weeks with N ω-nitro-L-arginine methyl ester in the drinking water (L-NAME-treated SHR, 6 mg
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