Effects of Bay K 8644 in aorta from spontaneously hypertensive and Wistar Kyoto rats of different ages.
1. The Ca(2+)-channel agonist, Bay K 8644, induced small contractions in aortae from Wistar-Kyoto (WKY) rats of 5-week-, 3-month-, 1-year- and 1.5-year-old, which were unaltered with age. These contractions were increased by partial depolarization with 15 mM K+. 2. In segments from spontaneously hypertensive rats (SHR), the contractions obtained in both situations were similar and equivalent to those observed in segments from normotensive animals partially depolarized. Responses to Bay K 8644 were modified by age only in tissues from the SHR, the responses to this agent in basal conditions being increased in tissues from 3-month- and 1-year-old animals and depressed in those from 1.5-year SHR. 3. A reduction of the response to Bay K 8644 was observed in partial depolarized endothelium denuded segments from WKY of all ages, and no modification in basal situation. However, the direct contractions induced by Bay K 8644 in aortae from 3-month- and 1.5-year-old SHR were reduced by endothelium removal. 4. These results suggest that: (a) in the hypertensive strain the voltage-gated Ca2+ channels seem to be partially activated; (b) the direct contractions induced by Bay K 8644 were unaltered by age in aortae from WKY but increased in tissues from SHR of 3-month-and-1-year old and depressed in those from 1.5 years, and (c) the contractions evoked by Bay K 8644 seem to involve an endothelium-derived contracting factor in aortae from both strains, or the endothelium produces a partial depolarization of vascular smooth muscle that increases the responsiveness to Bay K 8644.
Hernández
M C
MC
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Salaices
M
M
Ponte
A
A
Alonso
M J
MJ
Sánchez-Ferrer
C F
CF
Marín
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001685:Biological Factors; D002120:Calcium Channel Agonists; C067410:endothelium-dependent hyperpolarization factor; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester