Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats.
Endothelin, an endothelium-derived vasoconstrictor peptide, and angiotensin II were intravenously injected into the femoral vein of normotensive Wistar-Kyoto (WKY) rats that had been anesthetized with urethane. Blood pressure and heart rate were recorded from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. Endothelin showed a potent, dose-dependent pressor action. The dose-response relations for the increase in blood pressure of rats receiving endothelin were comparable with those of rats receiving angiotensin II. However, endothelin showed far more long-lasting effects. Endothelin-induced responses consisted of three phases: a rapid and transient depressor phase and then two phases of pressor (transient and long-lasting) response. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+ channel blocker, markedly attenuated the slow phase of the pressor response but only slightly attenuated the rapid one. The pressor action of endothelin was not inhibited by continuous infusions of saralasin, which almost abolished the angiotensin II-induced pressor response. Endothelin-induced pressor response was also not attenuated by indomethacin, a prostaglandin synthesis inhibitor. These data provide evidence that endothelin produces a unique, potent, and long-lasting pressor response, which appears to be in part related to the activation of Ca2+ channels. In 12-week-old spontaneously hypertensive rats (SHR), the maximal pressor response to endothelin was slightly but significantly greater than that in age-matched WKY rats, but the dose dependency of the response was approximately consistent with that in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Miyauchi
T
T
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Ishikawa
T
T
Tomobe
Y
Y
Yanagisawa
M
M
Kimura
S
S
Sugishita
Y
Y
Ito
I
I
Goto
K
K
Masaki
T
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009529:Nicardipine; D012504:Saralasin; D007213:Indomethacin