IMPAIRED VASODILATOR RESPONSE TO ATRIAL-NATRIURETIC-FACTOR IN IDDM

Diabetes mellitus has been associated with both elevated plasma concen trations of the natriuretic and vasorelaxant hormone atrial natriureti c factor and with a reduced natriuretic response to this hormone. We n ow hypothesize that the vasodilator response to atrial natriuratic fac tor is attenuated in IDDM. Forearm vasodilator responses to the infusi on of six increasing dosages of atrial natriuretic factor into the bra chial artery were registered by venous occlusion strain gauge plethysm ography in 10 patients with uncomplicated IDDM and in 10 age-, sex-, a nd weight-matched control subjects. Baseline levels of blood pressure, forearm blood flow, and plasma concentrations of atrial natriuretic f actor were not different between control subjects and patients with di abetes. In control subjects, atrial natriuretic factor induced a perce ntage fall in the forearm vascular resistance of -29 +/- 5% at the low est to -72 +/- 4% at the highest infusion rate. In patients with diabe tes this fall was significantly attenuated, measuring -2 +/- 7 and -45 +/- 4%, respectively, (P < 0.001 vs. control subjects). During infusi on of atrial natriuretic factor into the brachial artery, the calculat ed regional production of cGMP (second messenger of atrial natriuratic factor) increased from 1.2 +/- 1.1 to 22.8 +/- 4.8 pmol . min-1 . 100 ml-1 in the control subjects, whereas hardly any change occurred in t he patients with diabetes (from -2.1 +/- 1.2 to 2.9 +/- 4.7 pmol . min -1 . 100 ml-1). Furthermore, both control and diabetic subjects demons trated an equal forearm vasodilator response to increasing infusion ra tes of the control vasodilator sodium nitroprusside. We conclude that uncomplicated IDDM is associated with a specific reduction in the vasc ular responsiveness to atrial natriuretic factor. In association with the normal baseline plasma concentrations of this hormone, our results suggest that the contribution of circulating atrial natriuretic facto r to the baseline vascular tone is reduced in diabetic patients compar ed with healthy control subjects. This observation may be of relevance with respect to the regulation of blood pressure and vascular tone in patients with diabetes mellitus, especially in conditions with high b aseline levels of atrial natriuretic factor.