Angiotensin II-induced tachyphylaxis in aortas of normo- and hypertensive rats: changes in receptor affinity.
Angiotensin II-induced tachyphylaxis was found to be associated with changes in agonist affinity (Ka) and EC50 values, as assessed by using Furchgott's equation derived for the determination of full agonist affinity. The diminished affinity during tachyphylaxis was observed in aorta ring preparations from both Wistar-Kyoto and spontaneously hypertensive rats. Noradrenaline (10(-9) M) reduced the increase in the Ka value during tachyphylaxis in both strains. The results suggest that tachyphylaxis occurs at the level of the receptor, resulting in changes in the affinity of the ligand for the receptor and in the coupling efficiency of the receptor system. The results also support the probable role of modulators acting on allosteric receptor sites.
Kuttan
S C
SC
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Sim
M K
MK
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013618:Tachyphylaxis / Q000502:physiology*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009638:Norepinephrine