Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension.
We reported previously that simulating sleep apnea in rats by exposing them 7 hours per day to intermittent hypoxia/hypercapnia (IH) elevates plasma endothelin-1 and causes hypertension, which is reversed by an endothelin-1 antagonist. We hypothesized that in this model of sleep apnea-induced hypertension, vascular sensitivity to endothelin-1 is increased in combination with the elevated plasma endothelin-1 to cause the endothelin-1-dependent hypertension. In small mesenteric arteries with endothelial function disabled by passing air through the lumen, diameter and vessel wall [Ca2+] were recorded simultaneously. IH arteries demonstrated increased constrictor sensitivity to endothelin-1 (percentage max constriction 100+/-0% IH versus 80+/-10% Sham; P<0.05). This was accompanied by increased calcium sensitivity of IH arteries. In contrast, constrictor sensitivity and increases in vessel wall [Ca2+] to KCl and phenylephrine were not different between IH and Sham arteries. We have shown previously that endothelin-1 constriction in mesenteric arteries is mediated by endothelin A receptors. In the current study, the selective increase in endothelin-1 constriction in IH resistance arteries was accompanied by increased expression of endothelin A receptor expression (densitometry units 271+/-23 IH versus 158+/-25 Sham; P<0.05). Thus, IH hypertension appears to cause alterations in signaling components unique to endothelin-1 at the receptor level and in postreceptor signaling that increases calcium sensitivity during endothelin A activation. Future studies will determine the specific changes in vascular smooth muscle signaling in IH hypertension causing this augmented contractile phenotype.
Allahdadi
Kyan J
KJ
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico, Health Sciences Center, Albuquerque, NM 87131, USA.
Walker
Benjimen R
BR
Kanagy
Nancy L
NL
D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D012891:Sleep Apnea Syndromes / Q000150:complications; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D002118:Calcium