Endothelium-dependent vasodilation in the uvea of hypertensive and normotensive rats.
OBJECTIVE
The effects of endothelium-related substances such as acetylcholine, a stimulator of endogenous NO-production, the NO-synthesis inhibitor L-NMMA, the exogenous NO-donor sodium nitroprusside and the endothelin (ET)A-receptor antagonist BQ123, on uveal blood flow were investigated in normotensive and hypertensive SHR rats.


METHODS
The radioactively-labelled microsphere method was applied for the measurement of regional blood flow in the uvea.


RESULTS
Under resting conditions, local blood flow was lower in the hypertensive animals. The increase in choroidal blood flow (145 +/- 50%; P < 0.01) and reduction in vascular resistance (-58 +/- 7%; P < 0.01) observed in the WKY after i.v. infusion of acetylcholine, 2 micrograms x kg bw-1 x min-1, were significantly less pronounced in animals pretreated with L-NMMA, indicating local formation of NO as a vasodilator mechanism. In contrast, acetylcholine did not induce significant vasodilation in the choroid of SHR rats. In the anterior uvea of both strains, acetylcholine did not affect local blood flow. L-NMMA, 20 mg x kg bw-1, alone reduced blood flow in the entire uvea of both strains. Intravenous injection of BQ123, 1 mg x kg bw-1, did not affect regional blood flow in the uvea of WKY or SHR animals. Infusion of acetylcholine following ETA-receptor blockade induced vasodilation in both the choroid and anterior uvea in the WKY but not in the SHR.


CONCLUSIONS
Acetylcholine-stimulated NO-mediated vasodilation, but not basal NO-formation, was impaired in the choroid of the SHR. Furthermore, an interaction between vasoconstricting ET and acetylcholine was found in the anterior uvea of normotensive but not hypertensive rats.
Granstam
E
E
Department of Ophthalmology, University Hospital of Uppsala, Sweden. sven-olof.granstam@medicin.uu.se
Granstam
S O
SO
Fellström
B
B
Lind
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008863:Microspheres; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000502:physiology; D014602:Uvea / Q000098:blood supply*; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)