Nitric Oxide and Ocular Blood Flow in Patients With IDDM

Abstract

Endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disorders such as diabetic retinopathy. We hypothesized that either local endogenous nitric oxide (NO) synthesis or local reactivity to endogenous NO might be impaired in patients with IDDM and that this may contribute to the development of diabetic retinopathy. Ten otherwise healthy patients with long-standing IDDM and ten healthy control subjects were studied according to an open randomized two-way cross-over design. Subjects received intravenous infusions of either N(G)-monomethyl-L-arginine, an inhibitor of NO-synthase, or L-arginine, the precursor of NO synthesis, on two separate study days. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine decreased fundus pulsations and blood flow velocity in the ophthalmic artery and increased blood pressure in healthy subjects. The responses to NO-synthase inhibition were significantly less in diabetic subjects. In contrast, L-arginine caused a comparable increase in fundus pulsations and decrease in blood pressure in both cohorts. These results indicate that systemic and ocular hemodynamic reactivity to NO-synthase inhibition is reduced in patients with long-standing IDDM, compared with healthy control subjects. Thus, this study indicates that either NO-synthase activity is increased or NO sensitivity is decreased in patients with IDDM and supports the concept of an involvement of the L-arginine-NO system in the pathophysiology of diabetic retinopathy.

Abnormal retinal vascular function and lipid levels in a sample of healthy UK South Asians

“…While the exact aetiology of these vascular disturbances remains uncertain, it is possible that in our SA sample, the longer RT in the third flicker cycle represents an early sign of vascular dysfunction due to either a decreased bioavailability of NO21 or an exhaustion of the NO reserves after the first two flickering cycles. This abnormality could also signal a certain degree of vascular stiffness22 that is already present at the retinal vascular level in these individuals.…”

Ocular haemodynamics and colour contrast sensitivity in patients with type 1 diabetes

“…The reason for this early increase in pulsatile choroidal blood flow remains to be established. An altered endothelial function, as evidenced from an abnormal choroidal vascular response to a nitric oxide-synthase inhibitor,33 could well contribute to choroidal overperfusion. Glucose plasma levels had no significant impact on choroidal blood flow.…”

Hypertensive retinopathy revisited: some answers, more questions

“…44-50 L-NMMA reaction of retinal capillary flow is impaired in hypertensive patients 43 and in patients with type 1 diabetes a reduced response of choroidal flow to L-NMMA has also been observed. 51 Additionally, arteriolar narrowing and arteriovenous nicking were inconsistently associated with diabetes, glucose, and glycosylated haemoglobin. 28 In contrast, hypertensive retinopathy was strong and consistently associated with diabetes, its duration, and its severity.…”

“…[57][58][59] Among the various pathophysiological mechanisms, endothelial dysfunction has been implicated in the pathogenesis of the metabolic syndrome and points to a link between diabetes and hypertension. 60 61 It was observed 51 that systemic and ocular haemodynamic reactivity to NOsynthase inhibition is reduced in patients with long standing insulin dependent diabetes mellitus, compared with healthy control subjects The blunted response of retinal capillary flow to L-NMMA observed 43 in young hypertensive patients with essential hypertension indicates a reduced contribution of nitric oxide to the maintenance of retinal perfusion. 43 Therapy with AT1 receptor blocker candesartan celexitil restored both the contribution of nitric oxide to the maintenance of retinal perfusion and nitric oxide dependent vasodilation in the retinal vasculature of patients with arterial hypertension.…”