Dissociation between calcium influx blockage and smooth muscle relaxation by nifedipine in spontaneously hypertensive rats

G. J. Rinaldi, E. Amado Cattaneo, A. Mattiazzi, H. E. Cingolani

Research output: Contribution to journalArticlepeer-review

Abstract

Aortic smooth muscle isolated from spontaneously hypertensive rats (SHR) and normotensive, age-matched Wistar Kyoto rats (WKY) was precontracted by potassium chloride. The relaxant effect of nifedipine (NIF) was much more pronounced in SHR than in WKY, while the relaxation produced by nitroglycerin (NTG) was similar in both tissues. EC50s were (in - log | M | ) NIF:SHR 13.1 ± 0.4 and WKY 9.4 ± 0.2 (p < 0.05); NTG:SHR 7.35 ± 0.3 and WKY 7.26 ± 0.18 (NS). Aortas from SHR were less sensitive to the contractile effect of Ca2+ than their WKY controls (EC50 was 3.18 ± 0.03 in WKY and 2.76 ± 0.13 in SHR, p < 0.05). The relaxant effect of NIF was dissociated from its effect on Ca2+ influx in SHR aortas. NIF 10-0 M relaxed the muscle by 100% without producing Ca2+ influx blockage, and NIF 10-9 and 10- 8 M induced Ca2+ influx blockage while the muscle continued in the relaxed state. Chemically skinned aortic fibers from SHR were less sensitive to the contractile effect of Ca2+ than their normotensive (NR) controls (pCa for EC50 was 5.91 ± 0.05 in SHR and 6.20 ± 0.03 in NR, p < 0.05). NIF 10-10 M depressed the contractile response to Ca2+ significantly more in SHR than in NR skinned fibers (pCa for EC50 for 5.62 ± 0.09 in SHR and 6.07 ± 0.07 in NR, p < 0.05). These data suggest that (1) the more pronounced relaxant action of NIF on SHR aortas cannot be explained by its effect on Ca2+ influx, since both effects were dissociated in these vessels; and (2) the mechanism for NIF- dependent relaxation in SHR appears to be located not at the sarcolemmal but at some intracellular level. In this respect, a reduced calmodulin content in SHR arteries, along with an anticalmodulin action of NIF, could explain both the lesser sensitivity to Ca2+ and the greater sensitivity to NIF that was found in SHR aortas.

Original languageEnglish (US)
Pages (from-to)367-374
Number of pages8
JournalCirculation research
Volume60
Issue number3
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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