Control of oxidative stress in microcirculation of spontaneously hypertensive rats

Abstract

One mechanism for organ damage in individuals with arterial hypertension may be due to oxygen free radical production. This study was designed to localize free radicals in a microvascular network of mature spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Because glucocorticoids play a role in pressure elevation of SHRs, we investigated their role in microvascular free radical formation. Oxygen radical production in mesentery was detected by tetranitroblue tetrazolium reduction to formazan aided by digital light-absorption measurements. Formazan deposits were observed in the endothelial cells and lumens of all microvessels and in lymphatic endothelia but were fewer in tissue parenchyma. The formazan distribution in younger (14 -16 wk old) WKY rats and SHRs was heterogeneous with low values in capillaries and small arterioles/venules (Ͻ30 m) but enhanced deposits in larger venules. Adrenalectomy served to reduce the formazan density in SHRs to the level of WKY rats, whereas dexamethasone supplementation of the adrenalectomized rats caused elevation in the larger venules of SHRs. In older (40 wk old) SHRs, formazan levels were elevated in all hierarchies of microvessels. After pressure reduction was employed with chronic hydralazine treatment, the formazan deposits were reduced in all locations of the microcirculation in both WKY rats and SHRs. Elevated formazan deposits were also found in lymphatic endothelium. These results suggest that oxygen free radical production is elevated in both high-and lowpressure regions of SHR microcirculation via a process that is controlled by glucocorticoids. Older SHRs have higher formazan levels than younger SHRs in all microvessels. Chronic hydralazine treatment, which serves to reduce arterial blood pressure, attenuates tetranitroblue tetrazolium reduction in WKY rats and SHRs even in venules of the microcirculation, which has no micropressure elevation. Free radical production may be a more global condition in SHRs and may not be limited to arteries and arterioles. mesentery; arteriole; capillary; venule; superoxide; nitroblue tetrazolium; dexamethasone; Wistar-Kyoto; adrenalectomy; hydralazine ELEVATION OF ARTERIAL blood pressure is accompanied by a significant risk factor for cardiovascular complications such as stroke, myocardial infarction, atherosclerosis, or renal failure. But the mechanisms that lead to such vascular complications in hypertension are still uncertain. A number of studies indicate that elevated oxygen free radical production may play a role in experimental models of hypertension (12,23,25,26,29,36,44,47) and in human hypertensive individuals (21, 31). Oxygen free radicals such as superoxide, hydrogen peroxide, hydroxyl radical, or peroxynitrite may cause local vascular damage while at the same time producing the hallmarks of hypertension, i.e., increased vascular tone, reduced fluid shear stress response, and arterial pressure elevation (8,9,19,53).Free radicals in hypertension may be derived from a variety of cells in vivo...

Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats

“…However, hydralazine treatment may not be regarded as the best control for the BP-reduction effect based on the antioxidant effects of this vasodilator (3). In the present study, NaHS treatment caused a rather significant ROS reduction compared with hydralazine, suggesting that the added reduction in inhibition of remodeling provided by NaHS may be explained by an additional reduction in ROS levels.…”

Enhanced Matrix Metalloproteinase Activity in the Spontaneously Hypertensive Rat: VEGFR-2 Cleavage, Endothelial Apoptosis, and Capillary Rarefaction

“…As discussed previously [2], doxycycline blocks MMP-1, -2, -8, and -9 but also has other actions, including affinity to bivalent ions, antimicrobial activity, and serpinolytic activity. Even though several of the current results are supported by the use of alternative and more specific MMP inhibitors, there is a need for chronic MMP inhibition in the SHR with more specific inhibitors.…”

“…Besides an elevated arterial blood pressure, the spontaneously hypertensive rat (SHR) form of hypertension shows numerous microvascular complications, e.g. free radical production, insulin resistance, attenuated leukocyte adhesion to the endothelium, apoptosis, and enhanced organ injury [1,2,3,4,5]. Endothelial apoptosis causes capillary closure and rarefaction with loss of parenchymal cells [6].…”

Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo

“…Growing evidence points to the possibility that hypertension per se can increase O 2 Ϫ levels in various tissues (13,45,46), although other studies indicate hypertension is not invariably associated with increased O 2 Ϫ levels (36). Therefore, to test the hypothesis that S6c increases O 2 Ϫ levels in sympathetic ganglia in part by elevating blood pressure, we infused PE (10 g⅐kg Ϫ1 ⅐min Ϫ1 ) into conscious rats to produce an increase in blood pressure similar to that observed during S6c infusion.…”