Abstract
Vasoconstrictor effects of Bay K 8644 (an agonist known to increase Ca2+ influx through the voltage-dependent Ca2+ channels) on femoral arteries of 6 week old spontaneously hypertensive rats (SHR) were investigated, and data compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). The addition of Bay K 8644 (1 X 10(-10)-3 X 10(-7) M) elicited a dose-dependent contraction in SHR femoral artery in the absence of any contractile agent. Maximum contraction induced by this agonist was the same as the maximum induced by either K+-depolarization or alpha-adrenoceptor stimulation. Bay K 8644 was less effective in eliciting a contraction in the WKY femoral artery. Increased sensitivity to K+ was also observed in the SHR femoral artery. In contrast, contractions in response to alpha-adrenoceptor stimulation were the same in the SHR as those in the WKY. The addition of nifedipine, a Ca2+ channel antagonist, to an unstimulated preparation produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY. When the arteries were contracted with 60 mM K+, nifedipine produced similar relaxations in the SHR as those in the WKY, suggesting that the Ca2+ channels in the SHR femoral arteries are more activated than those in the WKY femoral arteries. Contractile responses to SHR femoral arteries to Bay K 8644 were antagonized competitively by nifedipine. Contractile responses to Ca2+ determined in K+-depolarized strips were also antagonized competitively by nifedipine. However, Schild plot analysis demonstrated a different pA2 value for nifedipine, suggesting that there may be a difference in the state of voltage-dependent Ca2+ channels in SHR femoral artery between the stimulation with Bay K 8644 and K+-depolarization.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Asano M., Aoki K., Matsuda T. Quantitative changes of maximum contractile response to norepinephrine in mesenteric arteries from spontaneously hypertensive rats during the development of hypertension. J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):727–731. doi: 10.1097/00005344-198407000-00028. [DOI] [PubMed] [Google Scholar]
- Asano M., Aoki K., Matsuda T. Reduced beta adrenoceptor interactions of norepinephrine enhance contraction in the femoral artery from spontaneously hypertensive rats. J Pharmacol Exp Ther. 1982 Oct;223(1):207–214. [PubMed] [Google Scholar]
- Asano M., Hidaka H. Pharmacological properties of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist in arterial strips from rats and rabbits. J Pharmacol Exp Ther. 1985 Aug;234(2):476–484. [PubMed] [Google Scholar]
- Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
- FURCHGOTT R. F., BHADRAKOM S. Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharmacol Exp Ther. 1953 Jun;108(2):129–143. [PubMed] [Google Scholar]
- Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
- Gopalakrishnan V., Park L. E., Triggle C. R. The effect of the calcium channel agonist, Bay K-8644 on human vascular smooth muscle. Eur J Pharmacol. 1985 Jul 31;113(3):447–451. doi: 10.1016/0014-2999(85)90095-0. [DOI] [PubMed] [Google Scholar]
- Hashimoto K., Takeda K., Katano Y., Nakagawa Y., Tsukada T., Hashimoto T., Shimamoto N., Sakai K., Otorii T., Imai S. Effects of niludipine (Bay a 7168) on the cardiovascular system with a note on its calcium-antagonistic effects. Arzneimittelforschung. 1979;29(9):1368–1373. [PubMed] [Google Scholar]
- Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
- Holloway E. T., Bohr D. F. Reactivity of vascular smooth muscle in hypertensive rats. Circ Res. 1973 Dec;33(6):678–685. doi: 10.1161/01.res.33.6.678. [DOI] [PubMed] [Google Scholar]
- Kanmura Y., Itoh T., Kuriyama H. Agonist actions of Bay K 8644, a dihydropyridine derivative, on the voltage-dependent calcium influx in smooth muscle cells of the rabbit mesenteric artery. J Pharmacol Exp Ther. 1984 Dec;231(3):717–723. [PubMed] [Google Scholar]
- Mikkelsen E., Nyborg N. C., Kazda S. A novel 1,4 dihydropyridine, BAY K 8644, with contractile effects on vascular smooth muscle. Acta Pharmacol Toxicol (Copenh) 1985 Jan;56(1):44–49. doi: 10.1111/j.1600-0773.1985.tb01251.x. [DOI] [PubMed] [Google Scholar]
- Mulvany M. J. Do resistance vessel abnormalities contribute to the elevated blood pressure of spontaneously-hypertensive rats? A review of some of the evidence. Blood Vessels. 1983;20(1):1–22. doi: 10.1159/000158455. [DOI] [PubMed] [Google Scholar]
- OKAMOTO K., AOKI K. Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 1963 Mar;27:282–293. doi: 10.1253/jcj.27.282. [DOI] [PubMed] [Google Scholar]
- Rosenberger L. B., Ticku M. K., Triggle D. J. The effect of Ca2+ antagonists on mechanical responses and Ca2+ movements in guinea pig ileal longitudinal smooth muscle. Can J Physiol Pharmacol. 1979 Apr;57(4):333–347. doi: 10.1139/y79-052. [DOI] [PubMed] [Google Scholar]
- Salaices M., Marin J., Sanchez-Ferrer C. F., Reviriego J. The effects of BAY-K-8644 on the contraction of cat middle cerebral and femoral arteries. Biochem Pharmacol. 1985 Sep 1;34(17):3131–3135. doi: 10.1016/0006-2952(85)90158-3. [DOI] [PubMed] [Google Scholar]
- Schramm M., Thomas G., Towart R., Franckowiak G. Activation of calcium channels by novel 1,4-dihydropyridines. A new mechanism for positive inotropics or smooth muscle stimulants. Arzneimittelforschung. 1983;33(9):1268–1272. [PubMed] [Google Scholar]
- Spedding M. Assessment of "Ca2+ -antagonist" effects of drugs in K+ -depolarized smooth muscle. Differentiation of antagonist subgroups. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):234–240. doi: 10.1007/BF00500485. [DOI] [PubMed] [Google Scholar]
- Su C. M., Swamy V. C., Triggle D. J. Calcium channel activation in vascular smooth muscle by BAY K 8644. Can J Physiol Pharmacol. 1984 Nov;62(11):1401–1410. doi: 10.1139/y84-233. [DOI] [PubMed] [Google Scholar]
- Uski T. K., Andersson K. E. Some effects of the calcium promotor BAY K 8644 on feline cerebral arteries. Acta Physiol Scand. 1985 Jan;123(1):49–53. doi: 10.1111/j.1748-1716.1985.tb07559.x. [DOI] [PubMed] [Google Scholar]
- Webb R. C., Bohr D. F. Recent advances in the pathogenesis of hypertension: consideration of structural, functional, and metabolic vascular abnormalities resulting in elevated arterial resistance. Am Heart J. 1981 Aug;102(2):251–264. doi: 10.1016/s0002-8703(81)80016-6. [DOI] [PubMed] [Google Scholar]
- Webb R. C., Vanhoutte P. M., Bohr D. F. Adrenergic neurotransmission in vascular smooth muscle from spontaneously hypertensive rats. Hypertension. 1981 Jan-Feb;3(1):93–103. doi: 10.1161/01.hyp.3.1.93. [DOI] [PubMed] [Google Scholar]
- Winquist R. J., Webb R. C., Bohr D. F. Vascular smooth muscle in hypertension. Fed Proc. 1982 Jun;41(8):2387–2393. [PubMed] [Google Scholar]
- Yamamoto H., Hwang O., Van Breemen C. Bay K8644 differentiates between potential and receptor operated Ca2+ channels. Eur J Pharmacol. 1984 Jul 20;102(3-4):555–557. doi: 10.1016/0014-2999(84)90581-8. [DOI] [PubMed] [Google Scholar]