Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 ± 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 ± 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 ± 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected. These rsults indicate that a nifedipine-sensitive, presumably extracellular, calcium pool is partly responsible for the pressor response induced by ET, whereas the response to AVP appears to depend upon activation of a nifedipine-insensitive, presumably intracellular, source of calcium. Furthermore, it can be suggested that, in vascular smooth muscle, ET activates a pertussis toxin-sensitive G-protein that is coupled to a receptor-operated calcium or nonspecific cation channel, whereas responses induced by AVP do not appear to be mediated through a G-protein that is sensitive to pertussis toxin.
|Number of pages||5|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1990|
ASJC Scopus subject areas
- Molecular Medicine