Summary
To examine the role of Ca channels in autoregulation of renal blood flow in response to changes of perfusion pressure, experiments were performed with perfused kidney in anesthetized dogs using a Ca channel activator, BAY K 8644, and vasoconstrictors such as noradrenaline and angiotensin II. Control observations usually showed excellent autoregulation of renal blood flow at pressures between 120 and 200 mm Hg, the autoregulatory index being less than 0.2. Verapamil (50 μg/min, i.a. infusion) obviously inhibited the renal autoregulation. Simultaneous infusion of 5 μg/min of BAY K 8644 with verapamil prevented both the increase of renal blood flow and the impairment of the autoregulation caused by verapamil. Whereas simultaneous infusion of noradrenaline (1 and 3 μg/min) or angiotensin 11 (0.1 and 0.3 μg/min) with verapamil dose-dependently reduced renal blood flow, these drugs could not antagonize the inhibitory effect of verapamil on autoregulation. The present experiments show that Ca channels play an important role in establishing renal autoregulation, and that a mere vasoconstriction by noradrenaline and angiotensin II is distinguished from autoregulatory performance.
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References
Baker S Jr, Cohen AJ, Fray JCS, Laurens NJ (1981) Role of calcium and albumin in the autoregulation of renal perfusate flow. J Physiol 311:1–9
Gross R, Kirchheim H, Brandstetter K (1976) Basal vascular tone in the kidney. Evaluation from the static pressure-flow relationship under normal autoregulation and at maximal dilation in the dog. Circ Res 38:525–531
Janis RA, Rampe D, Sarmiento JG, Triggle DJ (1984) Specific binding of a calcium channel activator, [3H]BAY K 8644, to membranes from cardiac muscle and brain. Biochem Biophys Res Commun 121:317–323
Mikkelsen E, Nyborg NCB, Kazda S (1985) A novel 1,4-dihydropyridine, BAY K 8644, with contractile effects on vascular smooth muscle. Acta Pharmacol Toxicol 56:44–49
Ogawa N, Kushida H, Satoh S (1984) Effect of verapamil on renal vasoconstriction induced by angiotensin II, norepinephrine or renal nerve stimulation in anesthetized dogs. Arch Int Pharmacodyn Ther 268:113–121
Ogawa N, Ono H (1985) No role for prostaglandins and bradykinin in the autoregulation of renal blood flow. Jpn J Pharmacol 39:349–355
Ogawa N, Ono H (1986a) Different effects of various vasodilators on autoregulation of renal blood flow in anesthetized dogs. Jpn J Pharmacol (in press)
Ogawa N, Ono H (1986b) Role of Ca channel in the renal autoregulatory vascular response analysed by the use of BAY K 8644. Naunyn-Schmiedeberg's Arch Pharmacol (in press)
Ono H, Kokubun H, Hashimoto K (1974) Abolition by calcium antagonists of the autoregulation of renal blood flow. Naunyn-Schmiedeberg's Arch Pharmacol 285:201–207
Schramm M, Towart R (1984) Modulation of calcium channel function with 1,4-dihydropyridine structure. J Physiol 349:53P
Schramm M, Thomas G, Towart R, Franckowiak G (1983) Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 303:535–537
Semple SJG, DeWardener HE (1959) Effect of increased renal venous pressure on circulatory autoregulation of isolated dog kidneys. Circ Res 7:643–648
Spedding M, Berg C (1984) Interaction between a “calcium channel agonist”, Bay k 8644, and calcium antagonists differentiate calcium antagonist subgroups in K+-depolarized smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 328:69–75
Takenaka T, Maeno H (1982) A new vasoconstrictor 1,4-dihydropyridine derivative, YC-170. Jpn J Pharmacol 32 (Suppl):139P
Thomas G, Chung M, Cohen CJ (1985) A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent. Circ Res 56:87–96
Thurau K, Kramer K (1959) Weitere Untersuchungen zur myogenen Natur der Autoregulation des Nierenkreislaufes. Pflügers Arch 269:77–93
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Ogawa, N., Ono, H. Different effects of noradrenaline, angiotensin II and BAY K 8644 on the abolition of autoregulation of renal blood flow by verapamil. Naunyn-Schmiedeberg's Arch. Pharmacol. 333, 445–449 (1986). https://doi.org/10.1007/BF00500022
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DOI: https://doi.org/10.1007/BF00500022