Low urinary kallikrein rats: different sensitivity of verapamil on hypertensive response to central acute cadmium administration.
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.
Varoni
Maria Vittoria
MV
DBA, Division of Pharmacology, Faculty of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Palomba
Domenico
D
Satta
Michele
M
Anania
Vittorio
V
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*
D000085:Acetates; D002121:Calcium Channel Blockers; D002104:Cadmium; C028031:cadmium acetate; D014700:Verapamil; D007610:Kallikreins