Abstract
BackgroundSpontaneously Hypertensive Rats (SHR) have chronically elevated blood pressures at 30 weeks of age (systolic: 191.0 ± 1.0, diastolic: 128.8 ± 0.9). However, despite this chronic malignant hypertension, SHR kidneys remain relatively free of pathology due to having an augmented myogenic constriction (MC). We hypothesized that the enhanced MC in the SHR preglomerular vessels was due to increased prostaglandin and decreased nitric oxide (NO) synthesis, providing renal protection.MethodsSHR and Wistar Kyoto (WKY) arcuate and mesenteric arteries were treated with indomethacin (prostaglandin synthesis inhibitor), N omega-nitro-L-arginine (L-NNA, NO synthase inhibitor), and nifedipine (L-type calcium channel blocker); and MC was measured in these vessels. The role of endothelium in MC was examined by removing endothelium from WKY and SHR preglomerular and mesenteric arteries using human hair, and measuring MC. We also studied the source of prostaglandin in the SHR by treating endothelium-removed arcuate arteries with indomethacin and furegrelate (thromboxane synthase inhibitor).ResultsMC was enhanced in the SHR preglomerular vessels but not the mesenteric arteries. Indomethacin and LNNA removed the enhanced MC in the SHR. Nifedipine also inhibited MC in both WKY and SHR arcuate and mesenteric arteries. Removing endothelium did not change MC in either arcuate or mesenteric arteries of WKY and SHR rats; and did not remove the augmented MC in the SHR arcuate arteries. Indomethacin and furegrelate decreased MC in endothelium-removed SHR arcuate arteries and obliterated the enhanced MC in the SHR.ConclusionThe enhanced MC in the SHR arcuate arteries was due to thromboxane A2 synthesis from the tunica media and/or adventitia layers. MC was not dependent on endothelium, but was dependent on L-type calcium channels. Nevertheless, SHR arcuate arteries displayed differential intracellular calcium signaling compared to the WKYs.
Highlights
In 1901, Bayliss observed that small resistant arteries from different vascular beds of rabbits, cats, and dogs decreased in diameter when he increased intraluminal pressure, and increased diameter with decreasing pressure
Spontaneously Hypertensive Rats (SHR) arcuate arteries demonstrated an enhanced myogenic constriction (MC) compared to the Wistar Kyoto (WKY) arteries (Figure 2C), and the augmented MC in the SHR was abolished by indomethacin treatment (Figure 2D)
We investigated the effects of blocking nitric oxide synthase (NOS) by LNNA on MC in the SHR and WKY rats
Summary
In 1901, Bayliss observed that small resistant arteries from different vascular beds of rabbits, cats, and dogs decreased in diameter when he increased intraluminal pressure, and increased diameter with decreasing pressure. It has been observed that some chronically hypertensive human (i.e., essential hypertensives) and rats (i.e., Spontaneously hypertensive rats, SHR) do not develop significant renal injuries despite highly elevated blood pressures. It appears that this renal protection is due to an augmented MC response in the pre-glomerular vessels (Arendshorst and Beierwaltes, 1979; Imig et al, 1996; Griffin et al, 2001; Loutzenhiser et al, 2002, 2004, 2006; Bidani and Griffin, 2004). We hypothesized that the enhanced MC in the SHR preglomerular vessels was due to increased prostaglandin and decreased nitric oxide (NO) synthesis, providing renal protection
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