title: Low urinary kallikrein rats: different sensitivity of verapamil on hypertensive response to central acute cadmium administration.
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.
authors.affiliation: DBA, Division of Pharmacology, Faculty of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Varoni
authors.forename: Domenico
authors.initials: D
authors.lastname: Palomba
authors.forename: Michele
authors.initials: M
authors.lastname: Satta
authors.forename: Vittorio
authors.initials: V
authors.lastname: Anania
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control; D007276:Injections, Intraventricular; D007610:Kallikreins / Q000187:drug effects / Q000378:metabolism* / Q000652:urine; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000085:Acetates; D002121:Calcium Channel Blockers; D002104:Cadmium; C028031:cadmium acetate; D014700:Verapamil; D007610:Kallikreins