Acute exposure to lead increases myocardial contractility independent of hypertension development

Abstract

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

Chronic Lead Exposure Increases Blood Pressure and Myocardial Contractility in Rats

“…Because of that these protocols were not performed. We evaluate the cardiac mechanical activity by hemodynamic records and isolated papillary muscles contraction and to access information about calcium influx we performed an indirect evaluation using the PRC protocol [20] .…”

“…To achieve the PRC, the calcium free solution was exchanged with by a modified Krebs solution (containing calcium, 1.25 mM) seconds before the beginning of electrical stimulation. The first contraction after rest was taken as an index of sarcolemmal calcium influx [20] .…”

Metalloproteinase Inhibition Protects against Reductions in Circulating Adrenomedullin during Lead‐induced Acute Hypertension

“…In support of this suggestion, it has been experimentally reported that blood lead concentrations at 19 lg/dL after 8 weeks [7] or 12 lg/dL after 4 weeks [8] or 9 lg/dL after 1 week [9] or 37 lg/dL after 2 hr [10] of lead intoxication were associated with sustained increases in blood pressure. Recently, some mechanisms have been proposed to explain why acute exposure to low lead concentrations are sufficient to cause lead-induced hypertension, such as increase in the angiotensin II levels due to angiotensin-converting enzyme activation [10], or increases in Na + /K + -ATPase activity and the expression of the a-1 subunits of Na + /K + -ATPase [9,11]. Thus, these alterations could be related with the deregulations of vascular tone.…”

Chronic Exposure to Low Doses of HgCl2 Avoids Calcium Handling Impairment in the Right Ventricle after Myocardial Infarction in Rats

“…To achieve post-rest contraction, the calcium-free solution was replaced with Krebs's solution (with 1.25 mM calcium) seconds before the electric stimulation. The first contraction after rest was taken as an index of the sarcolemmal calcium influx [28] .…”