Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM–100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM–300 µM) or sodium nitroprusside (0.01 nM–0.3 µM). Endothelium removal, N G-nitro-L-arginine methyl ester (100 µM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM) increased but losartan (10 µM) and enalapril (10 µM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na+/K+-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na+/K+-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na+/K+-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.

BackgroundChronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension.Methodology/Principal FindingsWistar rats were treated with lead acetate (i.v. bolus dose of 320 µg/Kg), and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na+,K+-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1) produced blood lead levels of 37±1.7 µg/dL, which is below the reference blood concentration (60 µg/dL); 2) increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg); 3) increased ACE activity (27% compared to Ct) and Na+,K+-ATPase activity (125% compared to Ct); and 4) did not change the protein expression of the α1-subunit of Na+,K+-ATPase, AT1 and AT2. Pre-treatment with an AT1 receptor blocker (losartan, 10 mg/Kg) or an ACE inhibitor (enalapril, 5 mg/Kg) blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg) did not prevent lead's hypertensive effect.ConclusionAcute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular disease.

Resistance training (RT) improves the cardiomyocyte calcium (Ca 2+) cycling during excitation-contraction coupling. However, the role of RT in cardiomyocyte contractile function associated with Ca 2+ handling in obesity is unclear. Wistar rats were distributed into four groups: control, sedentary obese, control plus RT, and obesity plus RT. The 10-wk RT protocol was used (4-5 vertical ladder climbs, 60-second interval, 3× a week, 50-100% of maximum load). Metabolic, hormonal, cardiovascular and biochemical parameters were determined. Reduced leptin levels, epididymal, retroperitoneal and visceral fat pads, lower body fat, and adiposity index were observed in RT. Obesity promoted elevation of collagen, but RT did not promote modifications of LV collagen in ObRT. RT induced elevation in maximum rates of contraction and relaxation, and reduction of time to 50% relaxation. ObRT group did not present improvement in the cardiomyocyte contractile function in comparison to Ob group. Reduced cardiac PLB serine 16 phosphorylation (pPLB Ser 16) and pPLB Ser 16 /PLB ratio with no alterations in sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a) and phospholamban (PLB) expression were observed in Ob groups. Resistance training improved body composition reduced fat pads and plasma leptin levels but did not promote positive alterations in cardiomyocyte contractile function, Ca 2+ handling and phospholamban phosphorylation.

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