Fos and nitric oxide synthase in rat brain with chronic mesostriatal dopamine deficiency: effects of nitroglycerin and hypoxia.

We found sustained proto-oncogene c-fos expression in neurons of the lateral and medial neostriatum and suppression of this expression in nitric oxide synthase (NOS)-containing cells within the islands of Calleja after lesions of the dopaminergic mesostriatal system induced by 6-hydroxydopamine. Systemic administration of nitroglycerin (NTG) or mild hypoxia resulted in a decreased of c-fos expression in the dorsolateral part of the denervated neostriatum. However, in other brain structures NTG or mild hypoxia evoked sustained c-fos expression in NOS-containing neurons and in the sources catecholaminergic projections involved in the control of cardiovascular function. We propose that the administration of NTG, an NO donor, or hypoxia partially attenuate the consequences of an excessively increased glutamate level in the denervated neostriatum which are manifest in high level of c-fos expression.

Phospholipid vesicles (liposomes) restore endothelium-dependent cholinergic relaxation in thoracic aorta from spontaneously hypertensive rats.

OBJECTIVE: The present study was designed to examine, using isolated preparations of thoracic aorta, the effects of artificial phosphatidylcholine vesicles (liposomes) on vascular endothelium-dependent responses in spontaneously hypertensive rats (SHR) compared with those in Wistar-Kyoto (WKY) normotensive rats. DESIGN: Phosphatidylcholine liposomes, which possess the ability to repair the plasma membrane of living cells, were used in these experiments. METHODS: Liposomes were prepared from egg phosphatidylcholine. A suspension of lipid was subjected to ultrasound treatment at 20 degrees C at a frequency of 44 kHz for 45 s. The contraction of vascular smooth muscle was recorded using a force-displacement transducer coupled with a physiograph. RESULTS: It was shown that aortic smooth muscle from SHR demonstrated a loss of endothelium-dependent relaxation in acetylcholine (10(-6) mol/l) compared with WKY rat aortic smooth muscle. Liposomes in a concentration of 100-125 micrograms/ml restored these endothelium-dependent responses more effectively than L-arginine (10(-5) to 10(-4) mol/l), which is known to be a precursor of endothelium-derived relaxing factor (EDRF). This effect was not observed in denuded aortic rings, and liposomes lost their ability of repairing endothelium-dependent vascular relaxant responses in the presence of methylene blue (5 x 10(-5) mol/l), which inhibits soluble guanylyl cyclase activation by nitric oxide (NO), and N omega-nitro-L-arginine (L-NNA, 5 x 10(-5) to 10(-4) mol/l), a potent and selective inhibitor of NO synthase. CONCLUSION: The present results suggest that the loss of vascular endothelium-dependent responses in SHR may be, at least partly, due to endothelial cells membrane damage, and that the phosphatidylcholine liposomes can repair the function of endothelial cells and restore synthesis or release, or both, of EDRF in hypertension.

Involvement of endothelium in vasodilating effects of vintoperol.

Experiments were performed on vessels of the femoral vascular bed of anesthetized dogs and on isolated rings of the rat pulmonary artery, vena cava, and thoracic aorta. Vintoperol was administered intra-arterially (0.01, 0.1, and 0.3 mg/kg/min for 10 min) or added in vitro (10(-4) M). De-endothelialization by saponin (0.5 mg/ml for 5 min) of intact vascular beds or mechanical endothelium removal in rings decreased vasodilation or relaxation by 50-60% vs. control. In de-endothelialized vascular beds, vintoperol (0.3 mg/kg/min) increased blood flow by 18 +/- 5% but 47 +/- 4% under control conditions (p < 0.05). Methylene blue (10 mg/kg) reduced the increment of blood flow to vintoperol from 47 +/- 4 to 24 +/- 4% (p < 0.05). After de-endothelialization of the isolated pulmonary artery, relaxation of precontracted segments was reduced (21 +/- 4% vs. 56 +/- 5% under control conditions; p < 0.05). Vintoperol-induced relaxation of vascular rings was also inhibited by gossypol (2 x 10(-5) M) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) depended on the duration of exposure to the inhibitors. In conclusion, relaxation to vintoperol must be mediated by the release of endothelium-derived nitric oxide.