Alpha-adrenoceptor-mediated pressor responses in pithed rats fed diets with different calcium contents.
Results of many clinical and experimental studies indicate an inverse relationship between dietary calcium and the prevalence of hypertension. Our study was designed to evaluate the alterations in arterial blood pressure and the changes in alpha-adrenoceptor-mediated vascular reactivity in normotensive Sprague-Dawley and spontaneously hypertensive rats (SHR) fed from weaning (3 weeks of life) three diets: normal calcium (Ca 1%), low calcium (Ca 0.1%), and high calcium (Ca 2.5%). The systolic and the diastolic arterial blood pressures were measured weekly by the tail cuff method. The plasma calcium levels in the animals were also measured regularly by colourimetric methods, and the alpha-adrenoceptor-mediated vascular reactivity was evaluated by measuring the pressor responses to alpha-adrenoceptor agonists in pithed rats. These determinations were carried out at the end of the feeding periods (9 weeks of life in Sprague-Dawley rats and 20 weeks of life in SHR) and also at the moments when maximal differences in arterial blood pressure were observed between the conscious animals fed the normal calcium diet and those fed the other two diets. Dietary calcium deficiency increased arterial blood pressure in both strains but calcium supplements were effective to lower this only in hypertensive animals. The plasma calcium levels were altered in both strains when calcium administration was not normal. The low-calcium diet did not modify the pressor responses to either the alpha(1)-adrenoceptor agonist, methoxamine, or the alpha(2)-adrenoceptor agonist, B-HT 920 (5-allyl-2-amino-5,6,7, 8-tetrahydro-4H-thiazolo-(4,5-D)-acepin-dihydrochloride, talixepole), in the normotensive and the hypertensive rats. On the contrary, the high-calcium diet caused a definite decrease in alpha(1)- and alpha(2)-adrenoceptor-mediated vascular reactivity in both strains. The changes in the alpha-adrenoceptor-mediated vasoconstrictor responses were observed in pithed 9-week old Sprague-Dawley rats and in pithed 20-week old SHR, but none were observed in pithed 15-week old SHR, although at this age maximal differences in arterial blood pressure between the animals fed the high- and the normal calcium diet were observed. The results of this study suggest that the mechanisms implicated in the effects of dietary calcium supplements on arterial blood pressure are clearly different from the mechanisms, which bring about changes in arterial blood pressure when the diet is deficient in calcium. The results of this study also show that calcium administration causes variations in alpha-adrenoceptor-mediated vascular reactivity, but this is probably not the only mechanism implicated in the calcium effect on arterial blood pressure.
Civantos
B
B
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense Madrid, C/Ciudad Universitaria, s/n 28040, Madrid, Spain.
López-Miranda
V
V
Ortega
A
A
Aleixandre de Artiñano
M A
MA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage*; D003655:Decerebrate State; D003971:Diastole; D004032:Diet; D004305:Dose-Response Relationship, Drug; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013599:Systole
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002136:Calcium, Dietary; D011942:Receptors, Adrenergic, alpha; C024763:talipexole; D008729:Methoxamine; D002118:Calcium