Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats
Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels.
- Research Organization:
- Univ. of Miami School of Medicine, FL
- OSTI ID:
- 6696136
- Journal Information:
- Am. J. Cardiol.; (United States), Journal Name: Am. J. Cardiol.; (United States) Vol. 3; ISSN AJCDA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALKALI METALS
ALKALINE EARTH ISOTOPES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BLOOD VESSELS
BODY
CALCIUM 45
CALCIUM ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CONTRACTION
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELEMENTS
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HORMONES
HYPERTENSION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MEMBRANE TRANSPORT
METALS
NEUROREGULATORS
NORADRENALINE
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
POTASSIUM
PYRIDINES
RADIOISOTOPES
RATS
RODENTS
STEROID HORMONES
SYMPATHOMIMETICS
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VASCULAR DISEASES
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