Impaired hemodynamics and endothelial vasomotor function via endoperoxide-mediated vasoconstriction in the carotid artery of spontaneously hypertensive rats.
The fact that endothelium removal increases diameter and compliance in the common carotid artery (CCA) of spontaneously hypertensive rats (SHR) and that improving CCA endothelium-dependent vasorelaxation has been shown to normalize a reduced systolic blood flow through the SHR CCA compared with normotensive Wistar-Kyoto rats (WKY) suggests that endothelial vasomotor dysfunction may be linked to altered large artery hemodynamics in hypertension. The experiments herein were designed to further investigate WKY and SHR CCA hemodynamics and endothelium-dependent vasomotor functions. It was hypothesized that CCA blood flow and conductance would be reduced throughout the cardiac cycle in SHR and that endothelium-dependent contractile activity would impair SHR CCA vasorelaxation. We report that mean, maximal systolic, and diastolic blood flow was reduced in SHR vs. WKY CCA, as was vascular conductance. Pressure was augmented in SHR CCA and accompanied by late systolic flow augmentation so that total flow during systole was indeed no different between strains, possibly explained by earlier lower body wave reflection. While ACh stimulation in isolated precontracted WKY CCA caused a robust nitric oxide (NO)-mediated vasorelaxation, endothelium-dependent, cyclooxygenase (COX)-mediated contractile activity stimulated by high ACh concentration impaired NO- and non-NO/non-COX-mediated vasorelaxation in precontracted SHR CCA. In quiescent CCA, this endothelium-dependent contractile response was COX-1 and thromboxane-prostanoid receptor mediated and modulated by the availability of NO. These data collectively suggest that endothelium-dependent, COX-mediated endoperoxide signaling in the CCA of SHR may elicit vasoconstriction, which could shift the mechanical properties of this conduit artery and contribute to reduced CCA blood flow in vivo.
Denniss
Steven G
SG
Integrative Vascular Biology Laboratory, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Rush
James W E
JW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D017536:Carotid Artery, Common / Q000502:physiology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017482:Receptors, Thromboxane / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D017482:Receptors, Thromboxane; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine