Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in arteries from young spontaneously hypertensive rats

Eur J Pharmacol. 1993 Nov 15;247(3):295-304. doi: 10.1016/0922-4106(93)90198-i.

Abstract

We examined whether the Ca2+ channel function in the resting state alters the resting tone in femoral and carotid arteries from spontaneously hypertensive rats (SHR) at early hypertensive stages (6 and 4 weeks of age), and data were compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). Strips of femoral and carotid arteries from 6-week-old SHR, but not from WKY, maintained a myogenic tone, that is, the resting tone decreased when 10(-7) M nifedipine was added. A similar myogenic tone was maintained in 4-week-old SHR. In strips of carotid arteries preloaded with fura-2, a fluorescent Ca2+ indicator, the decrease in cytoplasmic Ca2+ concentration following 0-Ca2+ solution or 5 x 10(-7) M nicardipine was significantly greater in SHR than in WKY. The basal 45Ca influx in femoral and carotid arteries from 6-week-old SHR was significantly increased when compared with WKY, and this increase in SHR was abolished by 10(-7) M nifedipine. The addition of charybdotoxin (a blocker of large conductance Ca(2+)-activated K+ channels) or of Bay k 8644 (an agonist of L-type voltage-dependent Ca2+ channels; VDCs), caused a concentration-dependent contraction, which was significantly greater in 6- and 4-week-old SHR than in WKY. These results suggest that the Ca2+ influx via L-type VDCs was increased in the resting state of femoral and carotid arteries from SHR at the early hypertensive stages, and therefore the myogenic tone was maintained and charybdotoxin-sensitive K+ channels were highly activated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Arteries / drug effects
  • Calcium / pharmacology*
  • Calcium Radioisotopes
  • Charybdotoxin
  • Electrophysiology
  • Fura-2
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Tonus / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Nifedipine / pharmacology
  • Potassium Channels / drug effects*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Scorpion Venoms / pharmacology

Substances

  • Calcium Radioisotopes
  • Potassium Channels
  • Scorpion Venoms
  • Charybdotoxin
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Nifedipine
  • Calcium
  • Fura-2