Increased vascular reactivity to Bay K 8644 in genetic hypertension

C. A. Bruner, R Clinton Webb

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

These experiments compared potential-operated calcium channel function in smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Carotid artery strips from adult male SHRSP and WKY rats were suspended in tissue baths for isometric force recording. Contractile force was expressed as percent of response to 100 mmol/l KCl. Vascular strips from SHRSP were more sensitive to KCl (ED50 = 25 mmol/l) compared to strips from WKY rats (ED50 = 37 mmol/l). The calcium channel agonist Bay K 8644 (2.8 x 10-10 to 2.8 x 10-7 mol/l) produced tonic contractions in carotid artery strips from SHRSP (34% of the contractile response to 100 mmol/l KCl) but not in those from WKY rats. Incubation of vascular strips in 1.8 or 6 x 10-10 mmol/l norepinephrine did not alter the maximal contractile response to Bay K 8644 in either strain of rats. In 12 mmol/l KCl, the maximal contractile response to Bay K 8644 was increased in both SHRSP (71%) and WKY rats (25%). In 18 mmol/l KCl, maximal contractile responses to Bay K 8644 in the two strains were similar (SHRSP = 73%, WKY = 76%). Removal of the endothelium did not significantly affect contractile responses to Bay K 8644 in either strain of rats. There were no differences in contractile responses of the calcium ionophore A23187 or in nifedipine-induced relaxation of potassium-activated vessels between carotid arteries from SHRSP and WKY rats. In summary, these results suggest that a difference in voltage-operated calcium channel function may underlie the increased sensitivity of SHRSP vascular smooth muscle to depolarizing stimuli.

Original languageEnglish (US)
Pages (from-to)24-35
Number of pages12
JournalPharmacology
Volume41
Issue number1
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Inbred WKY Rats
Blood Vessels
Hypertension
Carotid Arteries
Calcium Channels
Calcium Channel Agonists
Calcium Ionophores
Calcimycin
Inbred SHR Rats
Nifedipine
Baths
Vascular Smooth Muscle
Endothelium
Smooth Muscle
Norepinephrine
Potassium
Stroke

Keywords

  • Bay K 8644
  • calcium
  • endothelium
  • hypertension
  • nifedipine
  • vascular resistance

ASJC Scopus subject areas

  • Pharmacology

Cite this

Increased vascular reactivity to Bay K 8644 in genetic hypertension. / Bruner, C. A.; Webb, R Clinton.

In: Pharmacology, Vol. 41, No. 1, 01.01.1990, p. 24-35.

Research output: Contribution to journalArticle

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abstract = "These experiments compared potential-operated calcium channel function in smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Carotid artery strips from adult male SHRSP and WKY rats were suspended in tissue baths for isometric force recording. Contractile force was expressed as percent of response to 100 mmol/l KCl. Vascular strips from SHRSP were more sensitive to KCl (ED50 = 25 mmol/l) compared to strips from WKY rats (ED50 = 37 mmol/l). The calcium channel agonist Bay K 8644 (2.8 x 10-10 to 2.8 x 10-7 mol/l) produced tonic contractions in carotid artery strips from SHRSP (34{\%} of the contractile response to 100 mmol/l KCl) but not in those from WKY rats. Incubation of vascular strips in 1.8 or 6 x 10-10 mmol/l norepinephrine did not alter the maximal contractile response to Bay K 8644 in either strain of rats. In 12 mmol/l KCl, the maximal contractile response to Bay K 8644 was increased in both SHRSP (71{\%}) and WKY rats (25{\%}). In 18 mmol/l KCl, maximal contractile responses to Bay K 8644 in the two strains were similar (SHRSP = 73{\%}, WKY = 76{\%}). Removal of the endothelium did not significantly affect contractile responses to Bay K 8644 in either strain of rats. There were no differences in contractile responses of the calcium ionophore A23187 or in nifedipine-induced relaxation of potassium-activated vessels between carotid arteries from SHRSP and WKY rats. In summary, these results suggest that a difference in voltage-operated calcium channel function may underlie the increased sensitivity of SHRSP vascular smooth muscle to depolarizing stimuli.",
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