Stroke-prone SHR (SHRSP)
The SHRSP characteristically displays a more severe hypertension than the SHR. The SHRSP also demonstrates increase vascular reactivity to vasoconstrictor substances such as angiotensin II and noradrenaline, in comparison to normotensive Wistar rats (Berecek et al., 1980). The SHRSP have a higher renovascular resistance than the Wistar, which is apparent from an early age but becomes more pronounced after prolonged hypertension. An increased salt diet causes accelerated development of hypertension in both the SHR and SHRSP, however BP measurements have shown that SHRSP are more salt-sensitive than SHR and that may cause greater renal damage in SHRSP (Griffin et al., 2001). Nagaoka et al. (1981) reported that the SHRSP had autoregulatory control of renal blood flow (RBF) and glomerular filtration rate (GFR), which was operative over a higher BP range than that in Wistar rats (Nagaoka et al., 1981). When perfusion pressure was reduced so was the sodium and water Nocodazole of the SHRSP, therefore it appears that SHRSP requires higher than normal BP in order to efficiently excrete electrolytes and water. As well as the increased severity of hypertension in the SHRSP in comparison to the SHR, Churchill et al. (2002) showed that the SHRSP displayed other differences, namely increased intrinsic susceptibility to renal damage (Churchill et al., 2002). They proposed that there were genetic differences between SHR and SHRSP that accounted for the increased incidence of hypertensive lesions and malignant nephrosclerosis after only 4–6weeks on a high-salt diet, the SHR showed little tubular damage under similar conditions. The salt-induced kidney damage was thought to be not only linked to the increase in BP but also due to the vasculotoxic effects of salt (Griffin et al., 2001). In summary, the SHRSP have a higher BP level, increased tendency for renal damage and nephrosclerosis and are more salt-sensitive than SHR.
SHR and renal circulation
The SHR have characteristic differences in renal blood flow and renal function to the normotensive Wistar rat. These differences are due in part to structural changes namely, vascular remodelling caused by extracellular matrix deposition, hypertrophy and impaired vascular endothelium-dependent vasodilatation (Park et al., 2002). These factors cause a reduction in lumen diameter and increased peripheral resistance and therefore increased MAP. SHR display increased renal vascular resistance and increased reactivity to vasoactive substances such as noradrenaline and angiotensin II (Berecek et al., 1980). Stankevicius et al. (2002) showed that the arteries from hypertensive animals, contracted with noradrenaline, have decreased relaxation to acetylcholine (Stankevicius et al., 2002). This effect was proposed to be due to exposure of the arteries to the increased intraluminal pressure, because the extraluminal endothelium was found to be normal. The SHR have higher haematocrit levels and display increased platelet aggregation when exposed to thrombotic stimuli in comparison to normotensive Wistar rats (Lominadze et al., 1997).
Cowley et al. (1995) showed that in SHR compared to normotensive Wistar controls, renal MBP and sodium excretion were lower while cortical flow was similar (Cowley et al., 1995). These measurements were carried out using a laser Doppler flowmeter and indicated that MBP in SHR was reduced even before the appearance of hypertension. This apparent lower blood flow was accompanied by a raised vascular tone in the afferent arterioles of the juxtamedullary nephrons. With prolonged hypertension the cortex was also reported to become involved in the development of glomerular lesions and renal disease. In summary, the SHR have characteristic differences in renal blood flow and renal function to the normotensive Wistar rat. SHR display increased renal vascular resistance and increased reactivity to vasoactive substances. Also in SHR renal MBP is lower than that observed in normotensive control rats.
Stroke-prone SHR (SHRSP)