Different effects of calcium antagonists on fluid filtration of large arteries and albumin permeability in spontaneously hypertensive rats.
OBJECTIVE
To compare the effects of chronic administration of two dihydropyridines, nifedipine and amlodipine, and the non-dihydropyridine Ca2+ antagonist mibefradil on fluid filtration of large arteries and extravasation of albumin in spontaneously hypertensive rats.


METHODS
Spontaneously hypertensive rats aged 2 months were randomly allocated to oral treatment once a day with 30 mg/kg mibefradil (n=12), 100 mg/kg nifedipine (n=12), 20 mg/kg amlodipine (n=12) or placebo (n=12) for 1 month. Instantaneous blood pressure of rats under pentobarbital anaesthesia was recorded at the end of the treatment Fluid filtration across the carotid arterial wall was determined in situ in the isolated carotid artery. Extravasation of 25 mg/kg Evans Blue dye that had been injected intravenously was used to assess whole vascular permeability to albumin after chronic treatment with mibefradil.


RESULTS
Similar reductions in mean arterial pressure were obtained in all Ca2+ antagonist-treated rats. Heart rate was similar in rats in control, nifedipine and amlodipine groups but was significantly lower in mibefradil-treated rats (by 19%, P< 0.001). Fluid filtration across the carotid wall was greater in all Ca2+ antagonist-treated animals. However, fluid filtration was significantly less in mibefradil-treated rats than it was in nifedipine-treated, and amlodipine-treated rats. Furthermore, administration of mibefradil did not significantly modify extravasation of albumin in all tested tissues (pancreas, testis, spleen, lung, kidney, intestine, liver, skeletal muscle) except for cardiac and brain tissues, in which the permeability of albumin was increased by 24 and 33%, respectively, compared with values for the control group (P < 0.05).


CONCLUSIONS
These results indicate that Ca2+ antagonists increase fluid filtration through large arteries from spontaneously hypertensive rats. That the lower fluid filtration in mibefradil-treated rats was associated with no change in extravasation of albumin in most tissues and especially in skeletal muscle suggests that vascular permeability in hypertensive rats was impaired less by mibefradil treatment than it was by dihydropyridine Ca2+ antagonist treatments.
Lacolley
P
P
Institut National de la Santé et de la Recherche Médicale, U337, Paris, France.
Poitevin
P
P
Koen
R
R
Levy
B I
BI
D017311:Amlodipine / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000503:physiopathology*; D004487:Edema / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D020748:Mibefradil; D009543:Nifedipine / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012709:Serum Albumin / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D012709:Serum Albumin; D013764:Tetrahydronaphthalenes; D017311:Amlodipine; D020748:Mibefradil; D009543:Nifedipine