Impaired myogenic responsiveness of renal microvessels in Dahl salt-sensitive rats.

Abstract

The mechanisms mediating abnormal renal autoregulation in Dahl salt-sensitive (DS) rats have not been fully defined. In the present study, we assessed myogenic responsiveness of interlobular arteries (ILAs), afferent arterioles (AAs), and efferent arterioles in isolated perfused hydronephrotic Dahl rat kidneys. Dahl rats were divided into four groups according to strain (Dahl salt-resistant [DRI or the development of hypertension in DS rats. We have also demonstrated that in DS rats an impairment of the renal prostaglandin system contributes to blunted sodium excretion but not to abnormal glomerular hemodynamics.5To investigate further the mechanisms mediating abnormal glomerular circulatory behavior in DS rats, we carried out studies of renal microvascular responsiveness to increasing pressure in Dahl rats by using isolated perfused hydronephrotic kidneys. As detailed previously,6 this experimental model facilitates the examination of renal microvascular behavior in a controlled in vitro setting. Our current findings indicate that DS rats manifest blunted renal microvascular responsiveness to pressure when compared with DR rats, thereby contributing to the abnormal autoregulation of glomercular filtration rate observed in this strain. Materials and Methods General ProcedureMale and female Dahl rats were maintained on a low salt diet (0.2% NaCl, Teklad Premier Laboratory Diets, Madison, Wis.) and inbred in our animal facility. Experiments were carried out on 19 DR rats and 20 DS rats. After weaning, 4-5-week-old rats were used for induction of chronic hydronephrosis to permit direct visualization of the renal microcirculation. The right ureter was exposed by a small abdominal incision and ligated under methoxyflurane anesthesia (Metofane, Pittman-Moore, Mundelein, Ill.). Two or 3 weeks after surgery, seven DR and seven DS rats were placed on a

Role of 20-HETE in the antihypertensive effect of transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats

“…It also modulates tubuloglomerular feedback responsiveness, probably by affecting vascular reactivity to adenosine through modulation of K Ca channel activity (45). Indeed, this hypothesis is consistent with previous observations that the myogenic response (37) and dynamic autoregulation of RBF is impaired in Dahl S rats (14) and that TGF responsiveness is decreased when these rats are fed a HS diet (40).…”

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

“…47 These alterations in zonal hemodynamics within the kidney may be able to explain the observation that glomerular sclerosis is seen primarily in the juxtamedullary nephrons in SHR, despite the fact that whole kidney autoregulation is well preserved and the degree of total renal damage is much less than that seen in other hypertensive models, such as in Ang II-induced hypertension and Dahl salt-sensitive hypertensive rats. [48][49][50][51][52][53] The study of Mori et al 34 in Ang II-induced hypertension gives a strong support to the concept that hypertension itself causes tissue injuries primarily in the juxtamedullary cortex and outer medulla. Using the servo-control method, they kept perfusion pressure to the left kidney at a normotensive level, while inducing systemic hypertension by intravenous infusion of Ang II.…”

Enhancement of Intrarenal Angiotensinogen in Dahl Salt-Sensitive Rats on High Salt Diet

“…[25][26][27] It has also been shown that the myogenic responsiveness in DS rats is diminished. 28 Karlsen et al 29 reported that tubuloglomerular feedback responsiveness in hypertensive DS rats remained intact, which was not attenuated, as might be expected with reductions of intrarenal Ang II levels. Thus, these pathophysiological characteristics of intrarenal function in DS rats are consistent with an inappropriately enhanced AGT in the kidney, which may contribute to the development and maintenance of hypertension.…”