In acute experiments in spontaneously hypertensive (n=58) and normotensive (n=45) rats anaesthetized with urethane (1.7 g/kg, i.p.), we analysed the haemodynamic effects of activating and inhibiting nitric oxide (NO)-producing neurons within medullary nuclei which are known to participate in the cardiovascular control: nucleus tractus solitarius (NTS), paramedian reticular nucleus (PMn), nucleus ambiguous (AMB) and lateral reticular nucleus (LRN). We demonstrated that activation of neurons with unilateral injections of either a nitric oxide donor (sodium nitroprusside; 15.2-152 nmol), or a substrate for NO synthesis (L-arginine; 5.8-58.0 nmol) in most experiments resulted in lowering the systemic arterial pressure (SAP) level mainly due to a reduction in the peripheral vascular resistance which was more pronounced in hypertensive as compared with normotensive rats. The SAP was recorded from the femoral or carotid artery via an inserted polyethylene cannula, filled with heparinized 0.9% Ringer solution and connected with a pressure transducer and tensoamplifier. We recorded blood stroke volume (SV) using tetrapolar transthoracic impedance rheoplethysmography and calculated the cardiac output (CO) and peripheral vascular resistance (PVR). Injections of 5.8 nmol of L-arginine into the NTS of normotensive rats induced the lowering of the SAP by 18.4% (P<0.01) on average, those into the AMB by 23.8% (P<0.01), and those into the LRN by 18.2% (P< 0.05). Injections of 58.0 nmol of L-arginine into the NTS evoked a drop of the SAP by 29.4% (P<0.01), those into the AMB and LRN resulted in the SAP lowering by 25.2 and 29.8%, respectively (P< 0.01). In spontaneously hypertensive rats, injections of 58.0 nmol of L-arginine into the nuclei under exploration resulted in the SAP lowering by 39.8, 31.2 and 32.8% (P<0.01), correspondingly. Both NOS-1 and arginase are known to use L-arginine as a substrate for their metabolism and they can possibly compete for it. Therefore, we injected the NOS-1 antagonist (N^G-nitro-L-arginine; L-NNA, 4.6-23 nmol), and an antagonist for arginase (norvaline) into the medullary nuclei to see the contribution of those enzymes to the cardiovascular control in hypertensive rats. Our results indicated that both enzymes were potentially active. This suggests that L-arginine in medullary neurons of spontaneously hypertensive rats can be utilysed not only via NO-synthase pathway, but also via arginase-mediated metabolism of L-arginine. As such, a lack of L-arginine might contribute to the high level of the SAP. Injections of either inducters of mitochondrial permeability (MP) phenylarsine oxide (PAO, 10^-8 – 10^-12 M) or its inhibitors (cyclosporin A, melatonin, 10^-8 – 10^-12 M) into the medullary nuclei modulated the SAP level in a dose-dependent way. An increase in mitochondrial permeability induced a dose-dependent drop in the SAP level. Injections of inhibitors of MP induced dose-dependent changes in the SAP level; in normotensive rats the SAP level only slightly increased or decreased following injections of 10^-12 M melatonin, and the responses were prolonged. In spontaneously hypertensive rats, the responses of the SAP were similar to those in normotensive rats. However, prior administration of melatonin (10^-8 M, i.p.) enhanced the effects of injections of L-arginine. This suggests that inhibitors of MP can enhance the activity of the medullary NO-producing neurons during hypertension. Effects of NO-producing cardiovascular neurons were also modulated by injections of the superoxide dismutase into the medullary nuclei under exploration. The data obtained suggest that MP and an excess of superoxides in the medullary cardiovascular neurons may contribute to hypertension in rats.