Brain renin-angiotensin system modifies the blood pressure response to intracerebroventricular cadmium in rats.
In order to elucidate the involvement of the brain renin-angiotensin system (RAS) in cadmium intracerebroventricular (ICV) hypertension, we evaluated the effects of a pretreatment with different drugs: clonidine, an alpha(2) adrenergic agonist, enalapril and captopril, both ACE inhibitors, and saralasin, a competitive nonselective AT(1) and AT(2) receptor antagonist. We used a rat strain with low levels of kallikrein (LKR) that was more sensitive to ICV cadmium hypertension, compared with normal kallikrein rats (NKRs), the control strain. The interplay between the kallikrein-kinin system and the RAS in the LKR strain caused various hemodynamic alterations, which we believe were the result of elevated RAS activity in these animals. Moreover, we suggest that the defective kallikrein-kinin system in LKR may also cause an alteration in the activation of brain RAS in these animals. The LKR displayed elevated concentrations of plasma AII, hypertrophy of the myocardium, and initial alterations in the renal glomerulotubular system. With the exception of clonidine, all of the other drugs showed greater antihypertensive effects of differing statistical significance in LKR, compared with NKR. Both ACE inhibitors were able to significantly reduce pressor response to cadmium ICV in LKR throughout the experiment, whereas in NKR, they were only able to reduce the hypertensive peak of cadmium. A significant protective effect was also observed in LKR pretreated with saralasin, while no effect was observed in NKR. These findings confirm the presence of brain RAS activation in LKR and its contribution to the central control of pressor response to cadmium ICV.
Varoni
Maria V
MV
Department of Animal Biology, Division of Pharmacology, University of Sassari, Sassari, Italy. varoni@uniss.it
Palomba
Domenico
D
Macciotta
Nicolò P
NP
Antuofermo
Elisabetta
E
Deiana
Graziella
G
Baralla
Elena
E
Anania
Vittorio
V
Demontis
Maria P
MP
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D002104:Cadmium / Q000633:toxicity*; D002216:Captopril / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology; D006651:Histocytochemistry; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D016234:Kallikrein-Kinin System / Q000187:drug effects* / Q000502:physiology; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002104:Cadmium; D000804:Angiotensin II; D004656:Enalapril; D002216:Captopril; D007610:Kallikreins; D012504:Saralasin; D003000:Clonidine