ET-receptor function in relation to blood pressure in spontaneously hypertensive and aortic-banded rats.
Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, has been proposed to play a pathophysiologic role in hypertension. The aim of this study was to find out whether changes in ET-receptor function are cause or consequence of blood pressure elevation in hypertension. For this purpose, we assessed ET-receptor function [as ET-1-induced [3H]inositol phosphate (IP) accumulation] in slices of left ventricle and renal cortex and in rings of thoracic and abdominal aorta from spontaneously hypertensive rats (SHR) at the age of 8 weeks (i.e. developing hypertension), 12 and 24 weeks (established hypertension) vs. normotensive age-matched Wistar-Kyoto (WKY) rats, and from supra-renal aortic-banded (AOB) rats at the age of 8, 12 and 24 weeks (i.e. 4, 8 and 20 weeks after AOB) vs. sham-operated (SOP) age-matched WKY rats. In the SHR with established hypertension ET-1-induced IP formation was altered in all tissues investigated: it was significantly increased vs. WKY rats in left ventricle, and significantly decreased in renal and aortic tissues. Similarly, in AOB rats at all ages ET-1-induced IP formation was changed in those tissues that were under pressure load [heart (increase) and thoracic aorta (decrease)] vs. SOP rats, whereas in those tissues not under pressure load (kidney and abdominal aorta) ET-1-induced IP formation was not different between AOB and SOP rats. Moreover, in 8-week-old SHR (where hypertension is not yet established) ET-1-induced IP formation was not significantly different compared to WKY rats (with the exception of thoracic aorta). We conclude that, at least in SHR and AOB rats, changes in ET-1 signalling are secondary to the elevation in blood pressure.
Becker
K
K
Institute of Pharmacology and Toxicology, Martin Luther University of Halle-Wittenberg, Germany.
Heinroth-Hoffmann
I
I
Pönicke
K
K
Osten
B
B
Brodde
O E
OE
D000818:Animals; D001794:Blood Pressure; D019332:Endothelin-1 / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000502:physiology*; D013045:Species Specificity
D019332:Endothelin-1; D007295:Inositol Phosphates; D017466:Receptors, Endothelin