EFFECTS OF DIETHYLAMINE NITRIC-OXIDE ON BLOOD PERFUSION AND OXYGENATION IN THE R3230AC MAMMARY-CARCINOMA

The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short -acting nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous R3230Ac carcinoma in the leg. The effects of DEA/NO on the diameters of tumour-feeding and normal arterioles we re evaluated in window chambers with and without implanted tumours. DE A\NO reduced mean arterial pressure (MAP) when given at doses greater than or equal to 100 nmol kg(-1), with maximal suppression at 0.5-1 mi n followed by return to baseline within 20 min. DEA/NO did not affect MBF except at the highest doses (500 and 1000 nmol kg(-1)). In contras t, DEA/NO reduced TBF and constricted tumour arterioles at doses great er than or equal to 100 nmol kg(-1). Tumour arteriolar vasomotion occu rred in more than half the animals during hypotension and with a signi ficantly higher frequency than in normal granulating tissue at a dose of 500 nmol kg(-1), Normal arterioles rapidly and significantly vasodi lated for about 3 min and then returned to baseline, The reductions in TBF and MAP were accompanied by synchronous reduction in tumour pO(2) . Our findings suggest that DEA/NO decreases TBF in two ways. In the w indow chamber model, vascular steal occurs as normal arterioles adjace nt to tumour dilate more than tumour arterioles during the initial per iod of hypotension. In leg tumours, the predominant mechanism is attri butable to reduced perfusion pressure induced by lowered MAP, which de creases flow to the tumour, probably because of relatively higher flow resistance. The vasoconstriction and vasomotion in tumour arterioles during DEA/NO-induced hypotension may reflect differences in regulator y metabolism of NO between neoplastic and normal arterioles. Thus, int ravenous injection of a short-acting NO donor, DEA/NO, decreases MAP a nd heart rate, leading to subsequent decreases in tumour blood flow an d oxygenation.