Abstract Essential hypertension is a common disease caused by a combination of genetic and environmental factors. Cadmium (Cd), an important environmental pollutant, is able to induce hypertension in humans. In rats, intracerebroventricular (icv) Cd administration causes a sustained increase in arterial blood pressure. The kallikrein-kinin system appears an important regulator of cardiovascular function and rats with low renal excretion of kallikrein differ from normal-kallikrein Wistar rats in their pressor response to icv Cd. To clarify these differences in pressor response, we evaluated the protective effect of a calcium antagonist following the administration of 10 microg Cd icv. Pre-treatment with increasing doses of verapamil (100, 150200 microg) in normal-kallikrein rats produced a blocking of the hypertensive effects of Cd, even at the lower doses. In low-kallikrein rats we observed a dose-dependent inhibition of hypertensive effects at 100 and 150 microg, while at 200 microg there was, paradoxically, an increase in pressor values. Our results suggest that a genetically-determined defect in urinary kallikrein excretion leads to different modulation of brain calcium channels antagonists in the hypertensive response to icv Cd. This different sensitivity of low-kallikrein rats suggests that the hypertensive effect of icv Cd is, at least in part, the result of blocking the calcium channels, but is also sensitive to a new hemodynamic equilibrium, such as that present in low kallikrein rats, and probably intervenes as a modulator at the central level in other as yet not well identified systems, also linked to the hypotensive pathways, which may be activated in certain conditions.
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|Titolo:||Low urinary kallikrein rats: different sensitivity of verapamil on hypertensive response to central acute cadmium administration|
|Data di pubblicazione:||2003|
|Appare nelle tipologie:||1.1 Articolo in rivista|