Zn DEFICIENCY AGGRAVATES HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS: POSSIBLE ROLE OF Cu/Zn-SUPEROXIDE DISMUTASE

Abstract

Using spontaneously hypertensive rats (SHR) fed a standard or a Zn-deficient diet for 4 weeks, we examined whether Zn deficiency affects systemic blood pressure (BP) levels in a genetically hypertensive state through a fall in the activity of Cu/Zn-superoxide dismutase (SOD). SHR fed a Zn-deficient diet had a progressive increase in systolic BP during the dietary conditioning. Consequently, SHR fed a Zn-deficient diet exhibited significantly increased levels of systolic BP by 2 weeks after the start of dietary treatment when compared with SHR fed a standard diet. Similarly, levels of basal mean arterial pressure (MAP) observed at the end of dietary treatment were SHR fed a Zn-deficient diet > SHR fed a standard diet. Administration of the nitric oxide synthase (NOS) inhibitor, L-NAME, caused an increase in MAP levels in the two groups of rats, demonstrating the involvement of the vasodilator, nitric oxide (NO), in the regulation of systemic BP in a genetically hypertensive state. The expression of endothelial (e) NOS mRNA and protein in the thoracic aorta paralleled basal MAP levels in the two groups of rats, suggesting the counter-regulation of eNOS against the developed hypertensive state in SHR fed a Zn-deficient diet. On the other hand, administration of the superoxide scavenger, tempol (a SOD mimetic compound), led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in an increase in systemic BP in a genetically hypertensive state. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO, based on the formation of peroxynitrite coming from the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment completely restored MAP levels in SHR fed a Zn-deficient diet to levels comparable to those observed in SHR fed a standard diet, indicating that a further increase in systemic BP levels seen in SHR fed a Zn-deficient vs. a standard diet is presumably brought by a reduction in the action of the vasodilator, NO, resulting from an increase in the action of superoxide. The activity of the superoxide scavenger, Cu/Zn-SOD, in the thoracic aorta was significantly decreased in SHR fed a Zn-deficient diet relative to SHR fed a standard diet. It appears that a decrease in the activity of Cu/Zn-SOD observed in the thoracic aorta of SHR fed a Zn-deficient diet at least in part plays a role in an increase in the action of superoxide in this model. Thus, Zn deficiency may be a factor to develop genetic hypertension presumably through the oxidative stress caused by superoxide.

Control of oxidative stress in microcirculation of spontaneously hypertensive rats

“…The gender dimorphism with male SHRs presenting higher superoxide anion concentration under basal conditions than female SHRs may act via a mechanism that depends on NAD(P)H oxidase components (6). There could also be depletion of antioxidant enzymes (16,26,32,40,54). These enzyme systems can be modulated by renal and adrenal hormones, a situation that may be closely linked to the specific complications encountered in SHRs.…”

Antioxidant-Rich Diet Relieves Hypertension and Reduces Renal Immune Infiltration in Spontaneously Hypertensive Rats

“…Moreover, zinc deficiency has been shown to aggravate hypertension in SHR. 44 Given the natural origin of these nutrients, their low toxicity and ready availability, we elected to use this combination instead of more potent but less readily available and potentially toxic compounds, such as, lazaroid or tempol used in previous studies. 14,22 …”

Chromium (VI)-induced transformation is enhanced by Zn deficiency in BALB/c 3T3 cells

“…The reason of the limited protection might be by Cr(VI)-induced MTF-1 dysfunction in control and Zn-deficient medium plus MT-I/II -actin 50 μM Zn group. On the other hand, zinc-deficient culture causes not only a decrease in MTF-1-regulated gene expression, but also a decrease in Cu/Zn-superoxide dismutase (SOD) activity (Sato et al, 2002). Zinc has also been recognized as an intracellular second messenger (Murakami and Hirano, 2008;Prasad, 2014).…”