Effect of nos inhibition on retinal arterial and capillary circulation in early arterial hypertension.
BACKGROUND
Arterial hypertension is involved in the pathogenesis of end organ damage by influencing the ability of the vascular endothelium to produce nitric oxide (NO). This study analyzes changes of retinal and systemic NO-dependent circulation parameters by inhibiting nitric oxide synthase (NOS) in both hypertensive and normotensive individuals.


METHODS
In a double-blind crossover trial, 19 hypertensive patients (H, age 28.2 +/- 0.9 years) and 19 normotensive controls (N, age 26.9 +/- 0.9 years) were randomized treated either with candesartan or placebo. Both retinal capillary flow (RCF) and mean blood flow velocity of the central retinal artery (VCRA) were registered before and after NOS inhibition with N-monomethyl-L-arginine (L-NMMA, 3 mg/kg). In a subpopulation mean arterial pressure (MAP), cardiac output (CO), and the total peripheral resistance (TPR) were determined simultaneously.


RESULTS
Changes from baseline: In normotensive and hypertensive subjects infusion of L-NMMA led to an increase of MAP (N, +13.3 +/- 1.8%, P < 0.01; H, +14.3 +/- 2.4%, P < 0.01) and TPR (N, +36.9 +/- 3.8%, P < 0.01; H, +45.0 +/- 4.5%, P < 0.01), and to a decrease of CO (N, -21.1 +/- 1.5%, P < 0.01; H, -24.6 +/- 2.3%, P < 0.01). The L-NMMA effect on VCRA and RCF differed between controls and hypertensives. VCRA changed by + 17.3 +/- 6.2% (P < 0.05) and RCF by -7.3 +/- 3.0% (P < 0.05) in controls. In hypertensive subjects corresponding results were + 9.5 +/- 5.2% (P = NS) and + 2.7 +/- 3.8% (P = NS), respectively. The decrease of RCF due to L-NMMA was reduced in hypertension as compared to controls (P < 0.05). The calculated cross-sectional area of CRA was reduced by -58.7% in controls and increased by + 31.1% in hypertensive subjects. There was no significant correlation between the flow in the systemic and retinal circulation.


CONCLUSIONS
Only normotensives L-NMMA induces an acceleration of VCRA due to a probable vasoconstriction of the central retinal artery and despite of a reduced RCF. Already in early hypertension the NOS-dependent vascular tone in retinal arteries and capillaries is impaired. The regulation of the retinal capillary flow appeared to be independent from systemic circulation.
Michelson
Georg
G
Augenklinik mit Poliklinik, Universität Erlangen-Nürnberg, Schwabachanlage 6, D-91053 Erlangen, Germany. Georg.Michelson@rzmail.uni-erlangen.de
Wärntges
Simone
S
Harazny
Joana
J
Oehmer
Sebastian
S
Delles
Christian
C
Schmieder
Roland E
RE
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001775:Blood Circulation; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure; D002196:Capillaries / Q000502:physiology; D002302:Cardiac Output; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007262:Infusions, Intravenous; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012161:Retinal Artery / Q000502:physiology*; D013777:Tetrazoles / Q000627:therapeutic use; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D013777:Tetrazoles; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; C077793:candesartan cilexetil