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Aim: Vascular risk factors, and particularly vasospasm, are thought to play a part in the pathogenesis of normal pressure glaucoma (NPG). This study aimed to determine whether the function of systemic resistance arteries was altered in patients with NPG. Methods: Contractile and relaxant function was assessed in arteries dissected from gluteal fat biopsies (11 NPG, 12 control) using small vessel myography. Results: Responses to K₊ and noradrenaline were similar in patients and controls and were unaffected by endothelial removal. In contrast, responses to 5-hydroxytryptamine (5-HT; pD₂; 7.29 (SD 0.16) v 6.66 (0.19); p=0.03) and endothelin-1 (ET-1; pD₂, 9.12 (0.10) v 8.72 (0.13); p=0.03) were enhanced in arteries from patients with NPG. Removal of the endothelium enhanced responses to 5-HT (pD₂, 6.66 (0.19) v 7.66 (0.08); p=0.003) and ET-1 (pD₂, 8.72 (0.13) v 9.66 (0.39); p=0.02) in control arteries but not in those from patients. ET-1 mediated contraction in control and patient arteries was reduced in the presence of (10_-5 M) nifedipine. Endothelium dependent and independent relaxation was not impaired in arteries from patients. Conclusions: This study has identified dysfunction of the systemic vascular endothelial cell in patients with normal pressure glaucoma. The vascular endothelium modulates contractile responses to 5-HT and ET-1 in human subcutaneous resistance arteries but this effect is lost in patients with NPG, indicating a selective defect in agonist mediated release of endothelium derived vasodilators. Selective antagonists of 5-HT and ET-1 may, therefore, help to prevent vasospasm in patients with NPG.

Background & Aims: Impaired pressor function in cirrhosis may be specific to certain agonists and vascular territories. This investigation determined whether responses to arginine vasopressin (AVP) and 5-hydroxytryptamine (5-HT) were impaired in hepatic arteries from cirrhotic patients. Methods: Cumulative concentration-response curves were produced for AVP (10^-^1^1 to 3 x 10^-^6 mol/L), 5-HT (10^-^9 to 3 x 10^-^5 mol/L), and potassium chloride (2.5 -120 mmol/L) in hepatic arteries from liver donors (noncirrhotic) and recipients (cirrhotic). The receptor stimulated by AVP was identified using a V"1-receptor antagonist (d[CH"2]"5Tyr[Me]AVP) and a selective V"2-receptor agonist (desmopressin [DDAVP]). Results: Cirrhotic patients had a high heart rate (98 +/- 4 beats/min) and cardiac output (9.87 +/- 0.51 L/min) but low peripheral vascular resistance (711 +/- 35 dyn . s/cm^5). None of the arteries had a functional endothelium. Maximal contraction (but not sensitivity) to AVP was smaller (P = 0.0002) in hepatic arteries from recipients (34.03% +/- 3.42% KCl) than donors (60.69% +/- 5.56% KCl). 5-HT-mediated contraction was enhanced in recipient hepatic arteries (88.81% +/- 5.43% KCl vs. 71.63% +/- 4.46% KCl; P = 0.01), but sensitivities were similar (P = 0.20). KCl-mediated contractions were similar (P = 0.87) in both groups. Arteries did not respond to DDAVP, but d(CH"2)"5Tyr(Me)AVP produced a concentration-dependent rightward shift in the response to AVP. Conclusions: These results demonstrate a selective impairment of V"1 receptor-mediated contraction in denuded hepatic arteries from cirrhotic patients, suggesting an abnormality within the vascular smooth muscle. GASTROENTEROLOGY 2000;118:765-771

Background/aims Endothelium dependent vasodilatation is an important regulator of blood flow to the eye but its role has not been investigated in vessels supplying the ciliary body. This study assessed the role of the endothelium in modulating vasoconstrictor responses of the intraocular bovine anterior ciliary artery. Methods Bovine anterior ciliary arteries (n=33) were mounted in a myograph, containing physiological salt solution at 37°C, for isometric force measurement. Cumulative concentration-response curves were obtained to the constrictor agonists 5-hydroxytryptamine (5-HT), noradrenaline, phenylephrine, prostaglandin F _2α, endothelin-1, and KCl in both endothelium intact and denuded arteries. Results All vasoconstrictors produced sustained contractile responses which were unaffected by the removal of the endothelium. Responses to 5-HT were also unaffected by inhibition of nitric oxide synthase. Conclusion These results indicate that neither agonist stimulated nor basal release of nitric oxide from the endothelium modulates responses to vasoconstrictor agonists in the isolated bovine anterior ciliary artery when measured in a no flow isometric system.