Blood pressure and alpha-vascular reactivity in hypertensive rats treated with amlodipine and dietary Ca.
It has been suggested that the combination of dietary Ca and Ca2+ channel antagonists could have a synergic antihypertensive effect. In this study, 3-week-old male spontaneously hypertensive rats (SHR) were randomized into four groups of animals. Two of these groups were fed on a normal Ca diet (Ca 1%) and the other two groups were fed on a Ca-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in their drinking water. Systolic and diastolic arterial blood pressure were measured weekly in the rats, from the 6th week of life until the 25th week of life, by the tail-cuff method, and we also calculated the corresponding pulse pressure values (systolic blood pressure-diastolic blood pressure). Determination of plasma Ca levels by colourimetric methods, and measurement in pithed rats of the pressor responses to the alpha-adrenoceptor agonists methoxamine and B-HT 920 (5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-acepin-dihydrochloride, talixepole) were also performed using 16- and 23-week-old animals from the different groups. The Ca-enriched diet decreased systolic and diastolic blood pressure in SHR. Almodipine also decreased systolic and diastolic blood pressure in SHR, and this drug intensified the antihypertensive effect of the Ca 2.5% diet in the SHR between weeks 13 and 18. Nevertheless, in the 19- to 25-week-old SHR amlodipine antagonized the effect of dietary Ca on arterial blood pressure. A decrease in the pulse pressure was seen only in the 15- to 20-week-old SHR which had been simultaneously treated with dietary Ca and amlodipine. All the treatments used increased calcaemia, and the highest plasma Ca levels were obtained in the animals which had received the combined treatment with Ca and amlodipine. The responses to methoxamine and to B-HT 920 in the pithed 16-week-old SHR were similar in the four groups of animals. The responses to these agonists in the pithed 23-week-old SHR fed on the Ca-enriched diet were smaller than the corresponding responses in 23-week-old SHR of the untreated group. By contrast, the responses to these agonists were slightly higher in the pithed 23-week-old SHR which were treated with amlodipine than in the pithed 23-week-old SHR in the untreated group. Moreover, amlodipine partially reversed the effect of dietary Ca on alpha-vascular reactivity. According to our results, it would seem inadvisable to use dietary Ca with a Ca2+ channel antagonist with the aim of controlling arterial blood pressure.
Civantos
Beatriz
B
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain.
Aleixandre
Amaya
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002136:Calcium, Dietary / Q000494:pharmacology*; D003655:Decerebrate State / Q000503:physiopathology; D004032:Diet; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D001381:Azepines; D002121:Calcium Channel Blockers; D002136:Calcium, Dietary; D011942:Receptors, Adrenergic, alpha; D017311:Amlodipine; C024763:talipexole; D008729:Methoxamine; D002118:Calcium