Moderate Zinc Deficiency Influences Arterial Blood Pressure and Vascular Nitric Oxide Pathway in Growing Rats

Abstract

There is an increasing interest in the involvement of trace elements such as zinc in the pathogenesis of cardiovascular diseases. This study was designed to examine whether moderate zinc deficiency during growth influences blood pressure (BP) and vascular nitric oxide (NO) pathway. Three-week-old weaned male Wistar rats were randomly divided into two dietary groups and fed either a moderately zinc-deficient diet (zinc content 9 mg/kg; n ϭ 12) or a control diet (zinc content 30 mg/kg; n ϭ 12) for 60 d. The following were measured: systolic BP, nitrates and nitrites urinary excretion, urinary chemiluminescence intensity, NADPH-diaphorase activity in the thoracic aorta and intestinal arterioles, and NO synthase (NOS) catalytic activity using L-[U14C]-arginine as substrate in the thoracic aorta. Zinc deficiency during growth induced an increase in BP from day 30 of the experimental period, leading to hypertension on day 60. Animals that were fed the zinc-deficient diet had lower urinary excretion levels of nitrates and nitrites and higher intensity of spontaneous luminescence on day 60. At the end of the experiment, zinc-deficient rats showed decreased NADPH diaphorase activity in endothelium and smooth muscle of the thoracic aorta and intestinal arterioles and decreased activity of NOS in thoracic aortic tissue. An imbalance in zinc bioavailability during postnatal and growing periods may be may be a risk factor in development of cardiovascular alterations in adult life. The mechanisms involved may include an impaired vascular NO system as a result of decreased NOS activity and higher systemic oxidative stress. Moderate and marginal zinc deficiency is by far more common than severe deficiency, especially in infants, children, and pregnant women in developing and developed countries, as a result of imbalances between intake and increased requirements (1,2). Zinc is an essential trace element required by all living organisms for many physiologic functions, including growth, development, and reproduction (3). Zinc has been documented to act as an antioxidant, to have membranestabilizing properties, to block apoptotic cell death, and to be essential for endothelial integrity (4 -6). Intracellular zinc is associated with proteins, primarily via complex interactions with cysteines, acting as an integral component of numerous metalloenzymes, structural proteins, and transcription factors (1,7).There is increasing interest in possible involvement of trace elements such as zinc in the pathogenesis of cardiovascular diseases (8). Many enzymes that are involved in the regulation of arterial blood pressure (BP), such as nitric oxide (NO) synthase (NOS), angiotensin-converting enzyme, and neutral endopeptidases, contain zinc in their structure (9 -11). The NOSs are a family of enzymes that catalyze the synthesis of NO and L-citrulline from L-arginine in the presence of NADPH and O 2 . The NOS family consists of three isoforms that are expressed in many tissues, including endothelium and vascular

Zinc deficiency during growth: Influence on renal function and morphology

“…As reported previously, rats fed a moderate zinc-deficient diet showed a significant fall in plasmatic, urinary and fecal levels, indicating that the diet was successful to induce a moderate zinc deficiency (Tomat et al, 2005). Moreover, kidney zinc concentration was lower in ZD rats compared with C rats (C = 27.63 ± 1.99 vs. ZD = 22.40 ± 0.77 ⁎ μg/g tissue, ⁎ p b 0.01).…”

“…We previously showed that ZD diet group exhibited higher levels of systolic blood pressure from day 30 (C: 114 ± 4 vs. ZD: 131 ± 3 mm Hg, p b 0.001) up to the end of dietary treatment compared with the C group (C: 122 ± 3 vs. ZD: 150 ± 3 mm Hg, p b 0.001) (Tomat et al, 2005).…”

“…We reported that the animals, exposed to a moderate zinc deficiency during growth, exhibited higher levels of systolic blood pressure from day 30 after initiation of the dietary treatment compared with the C group, reaching values over 140 mm Hg in the adult stage of life. This increase in arterial blood pressure was associated with a decrease in NOS activity in the endothelium and the smooth muscle of the aorta and arterioles and with a higher systemic oxidative stress (Tomat et al, 2005). The impairment in the vascular NO pathway could alter the normal balance between vasodilator and vasoconstrictor factors leading to an increase in vascular tone and hypertension.…”

“…In a previous study we demonstrated that moderate zinc deficiency during growth induced an increase in blood pressure associated with an impaired vascular nitric oxide (NO) system and/or higher systemic oxidative stress (Tomat et al, 2005).…”

“…Taking into account that there are not enough reports studying the renal effects of moderate zinc deficiency in growing animals, we investigated the effects of moderate zinc deficiency during growth on the renal morphology and function and on the renal nitric oxide system in adult life in the same experimental model (Tomat et al, 2005).…”