Non-invasive tests of neurovascular function: reduced axon reflex responses in diabetes mellitus of man and streptozotocin-induced diabetes of the rat.

The prevalence of neuropathy and microangiopathy complicating diabetes mellitus led to our development of non-invasive tests of neurovascular function. On the foot dorsum of consenting normal subjects, diabetic patients, normal and streptozotocin-induced (STZ) diabetic rats, transcutaneous electrical nerve stimulation (TENS) with 1, 2, 4, 8, 16 pulses at 150 V, 0.75 ms, at 2 Hz, evokes transient cutaneous axon reflex vasodilatation measured by a laser Doppler (Periflux Pfld). This tests the integrity of both the polymodal nociceptor/primary afferent nerves and microvessels in the skin. TENS-evoked axon reflexes are reduced in diabetics (particularly with neuropathy) and progressively in rats 40-100 days after STZ administration. This could be reversed in rats by a single injection of 3 units of soluble insulin at 100 days post STZ. The microvascular endothelium and smooth muscle are tested in man by measuring vasodilatation induced by iontophoretic application of 2 mC acetylcholine (ACh) and 4 mC sodium nitroprusside (NaNP), respectively. Diabetics show reduced ACh-evoked endothelium-dependent vasodilator responses, but the direct smooth muscle (endothelium-independent) responses evoked by NaNP are not reduced. Such functional neurovascular disturbances probably underlie many complications of diabetes mellitus, and the potential for these to be reversible with appropriate therapy can now be examined with such neurovascular tests.