Contractile responses to Bay K 8644 in rats with coarctation-induced hypertension.

Abstract

This study examines potential-operated calcium channel function in rats made hypertensive by aortic coarctation. The hypothesis that channel function is influenced by elevated arterial pressure was tested by comparing contractile responses to elevated K+ and to the potential-operated calcium channel agonist, Bay K 8644, in aortic segments above (thoracic) and below (abdominal) the coarctation that are exposed to hypertensive and normotensive pressures, respectively. To control for vessel differences, the effects of Bay K 8644 were also examined in abdominal aortae from two-kidney, one-clip hypertensive rats. Sensitivity to K+ (EC15) was significantly greater in both thoracic and abdominal aortae from coarctation-hypertensive rats than in those from normotensive sham rats. In the thoracic aorta, maximal contractile response to Bay K 8644 (normalized to contraction produced by 100 mM K+) was significantly greater in coarctation-hypertensive rats (124 +/- 9%) than in sham rats (12 +/- 6%). However, Bay K 8644 did not elicit contraction in abdominal aortae from either group. When [K+]o was increased (19.2 mM), thoracic aortae from coarctation-hypertensive rats were more sensitive to Bay K 8644, but there were no differences in maximal responses among thoracic and abdominal aortae. Bay K 8644 evoked dose-dependent contraction in all abdominal aortic strips from two-kidney, one-clip hypertensive rats (maximum = 68 +/- 11%). In summary, vascular responsiveness to Bay K 8644 is increased in the thoracic but not abdominal aorta from coarctation-hypertensive rats, whereas sensitivity to elevated K+ is increased in both vessels. Enhanced K+ sensitivity in the abdominal aorta may be related to general effects of the cation on membrane potential. However, augmented responsiveness to Bay K 8644 suggests a specific alteration in the function of potential-operated calcium channels that is dependent upon elevated blood pressure and is not due to differences in responsiveness between the thoracic and abdominal aortae.

• Authors: D S Storm, R C Webb
• Journal: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (Proc Soc Exp Biol Med) Vol. 203 Issue 1 Pg. 92-9 (May 1993) ISSN: 0037-9727 [Print] United States
• PMID: 7682719 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester

Topics

• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester (pharmacology)
• Animals
• Aorta, Abdominal (drug effects, physiology, physiopathology)
• Aorta, Thoracic (drug effects, physiology, physiopathology)
• Aortic Coarctation (physiopathology)
• Dose-Response Relationship, Drug
• Hypertension, Renovascular (physiopathology)
• In Vitro Techniques
• Male
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (drug effects, physiology, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Reference Values
• Renal Artery