The effect of losartan on calcium uptake by bovine aortic media in vitro.

The action of losartan, an AT1-angiotensin II receptor antagonist, on Ca2+ uptake by bovine aortic media in vitro was studied. This action was compared with that of nifedipine, a Ca2+ entry blocker. Ca2+ uptake values were obtained by measuring small slices of thoracic aorta tissue incubated in Kreb's solution in the presence of 45Ca. After preparation stimulation with angiotensin II (10 microM), losartan (1 microM and 10 microM) was shown to have a weaker inhibiting effect on Ca2+ uptake than nifedipine in equal concentrations. It is known that angiotensin II contracts smooth muscle by mobilizing intracellular Ca2+. The stimulating action on Ca2+ entry might be a secondary mechanism, which was studied for the first time in tissue slices derived from the aorta media. Results seem to be reasonable, since nifedipine also inhibited the spontaneous entrance of Ca2+, while losartan's action was focused only on the effects of angiotensin II.

Comparison of felodipine and nitroglycerin actions on vasomotion physiology.

Felodipine is a Calcium blocker and nitroglycerin, a nitrate vasodilating agent, were compared. Two parameters were studied in vitro on bovine aortic media. Calcium uptake and vascular tone. The Calcium uptake measurement was performed by incubating in Krebs solution small slices of the preparation in the presence of 45Ca. Studies on vascular tone were performed on deendothelialized bovine aortic rings suspended in Krebs solution. Felodipine (1nM-100microM) decreases Ca2+ uptake and relaxes the preparation while nitroglycerin's 1nM-100microM) action is also inhibiting but very weak. When the preparation is stimulated by alpha 1-adrenergic against phenylephrine 1microM, then nitroglycerin 100microM has a much stronger inhibiting effect on Call uptake and vascular tone than felodipine 100microM. These results are reversed when the preparation is stimulated by KC165.4mM. Then felodipine 100nM exerts a strong inhibiting effect on Ca2+ uptake and vascular tone while nitroglycerin's 100nM inhibiting action is very weak. It is well known that in cases of endothelium disfunction the adrenergic stimulation provokes vasoconstriction and ischemia. This ischemia induces a second phase of vasoconstriction that is due to a depolarization provoked by the increased levels of extracellular K+. Felodipine is able to antagonize the consequences of such a depolarization. Thus, felodipine may be useful as an additional agent to nitroglycerin's treatment and that is the clinical message of our findings.

Clonidine and vasomotion physiology.

It is known that clonidine exerts a hyperpolarizing action and alpha 2-adrenergic activity. The experimental work investigates the conditions under which each action of clonidine is developed on vascular smooth muscle. Two parameters were studied in vitro on bovine aortic media, Ca2+ uptake and vascular tone. The Ca2+ uptake measurement was performed by incubating in Krebs' solution small slices of the preparation in the presence of 45Ca. Studies on vascular tone were performed on deendothelialized bovine aortic rings suspended in Krebs' solution. Low concentrations of clonidine (1 nM-1 microM) decrease Ca2+ uptake and relax the preparation, indicating dominance of the inhibiting action of clonidine may be due to an hyperpolarization. Clonidine 10 microM results in equalization of the opposing actions of Ca2+ uptake and vascular tone. When the preparation is stimulated by alpha 1-adrenergic against phenylephrine 1 microM, clonidine 1 nM-10 microM potentates the Ca2+ uptake and vascular contraction in a monophasic way, indicating that the depolarizing mechanisms connected with the alpha 1-adrenergic stimulation totally inhibit the relaxing action of clonidine possibly due to hyperpolarization. This action is restricted in the presence of yohimbine (alpha 2-adrenergic blocker).

Felodipine and vasomotion physiology.

This study concerns the investigation of felodipine's influence on some parameters of vasomotion physiology. Felodipine is a new generation 1,4 dihydropyridine (1,4 DHP) Ca(2+)-entrance blocker with marked vascular selectivity. It was found that felodipine 1-10 microM presents a Ca2+ entrance-blocking activity when the bovine aortic smooth muscle is normal or stimulated by K+ 65.4 mM or the alpha-adrenoceptor agonist phenylephrine 1 microM. The same action is observed after nifedipine, a first-generation 1,4 DHP derivative with less angioselectivity in clinical practice. It was also found that felodipine 1-10 microM antagonizes the contraction of the bovine aortic ring that is induced by phenylephrine 10 microM or KCl 65.4 mM. On the contrary, felodipine 1-10 microM increases the contraction of the rat aortic ring that is induced by the same substances. It is known that some 1,4 DHP derivatives that are Ca2+ activators can also behave as Ca2+ blockers and that their final action is dependent upon membrane potential. Now it is also proved that the kind of animal species may also influence the action of the 1,4 DHP derivatives. It was finally found that felodipine increases the catecholamine stores of the sympathetic nerve terminal at the mouse heart (H) and liver (L). Obtained values were as following: control 15.00 +/- 7.7 (H) and 17.72 +/- 3.5 (L). Felodipine 54.50 +/- 4.9 (H) and 41.54 +/- 10.4 (L). Since catecholamine stores depend on secretion (Ca(2+)-dependent) and reabsorption (mostly Na(+)-dependent) rates, the increase after felodipine may be attributed to a decreased secretion due to a Ca2+ entry inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of methionine-5-enkephalin on calcium uptake by the bovine aortic media.

The influence of methionine-5-enkephalin (M-5-E), an endogenous opioid receptor agonist, on calcium uptake by bovine aortic media was investigated in vitro. 45Ca was used and radioactivity was counted in a beta scintillation counter. M-5-E increases Ca2+ uptake by the preparation. This action is inhibited by naloxone and that is proof that an opioid receptor is stimulated. A comparative study showed that phenylephrine, an alpha-adrenoceptor agonist, exhibits the same action as M-5-E, whereas morphine's action is negligible. Phenylephrine contracts the deendotheliazed ring of the bovine aorta, whereas M-5-E fails to do so. It is concluded that an opioid receptor was identified at the bovine aortic smooth muscle. This receptor is stimulated by M-5-E resulting in an increase of the extracellular Ca2+ entrance. Although no relationship was observed between the receptor and the contraction mechanism, a possible role of M-5-E in the maintenance of the vascular tone cannot be excluded.

The influence of amikacin on digoxin uptake by certain rabbit tissues in vitro.

The influence of amikacin on digoxin uptake by various rabbit tissues was investigated in vitro. 125J-digoxin was used and radioactivity was counted in a gamma scintillation counter. Amikacin decreases digoxin uptake by the renal tissue and this action is probably due to a displacing effect. On the contrary, amikacin increases digoxin uptake by striated and cardiac muscle. It is suggested that the latter action is due to a vasodilating effect of the aminoglycoside antibiotic that favors the microcirculation of the above tissues.