No abstract

Additional LVZ-based substrate modification after PVI improved the outcome in PeAF patients with LVZs, whereas PVI alone worked in patients without LVZs, even in those with PeAF.

Abstract-The role of nitric oxide (NO) in the brain in the control of blood pressure and the sympathetic nervous system is debated. This study examined the effect of overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarii (NTS) on blood pressure in conscious rats. Adenovirus vectors encoding either eNOS (AdeNOS) or ␤-galactosidase were transfected into the NTS in vivo. In the AdeNOS-treated rats, the local expression of eNOS in the NTS was confirmed by immunohistochemical staining and Western blot analysis for the eNOS protein and by increased production of nitrite/nitrate in the NTS measured by in vivo microdialysis. Blood pressure and heart rate, monitored by the use of a radiotelemetry system in a conscious state, were significantly decreased in the AdeNOS-treated group at day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion also was decreased at day 7 after the gene transfer in the AdeNOS-treated group. Our results indicate that overexpression of eNOS in the NTS decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats. (Hypertension. 2000;36:1023-1028.)Key Words: genes Ⅲ nitric oxide Ⅲ brain Ⅲ sympathetic nervous system T here is considerable evidence that nitric oxide (NO) in the brain affects sympathetic nerve activity and modulates blood pressure and heart rate. [1][2][3][4][5][6] Studies that used immunohistochemistry for neuronal NO synthase (nNOS), nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, have demonstrated the presence of nNOS at a high concentration in the regions of the brain stem, such as the nucleus tractus solitarii (NTS) and the ventrolateral medulla (VLM), which plays an important role in regulation of sympathetic nerve activity. 7,8 However, conflicting results have been obtained with regard to the effect of NO in the regulation of blood pressure and sympathetic nerve activity. Several studies have demonstrated that unilateral microinjection of the NOS inhibitor N G -monomethyl-L-arginine (L-NMMA) into the NTS produced the pressor effect, 1,2 and L-arginine, the precursor of NO, decreased blood pressure, heart rate, and renal sympathetic nerve activity. 2 On the contrary, the other study has shown that the microinjection of N -nitro-L-arginine methyl ester (L-NAME), another NOS inhibitor, into the NTS decreased blood pressure, heart rate, and renal sympathetic nerve activity, 3 and the NO donor Et 2 N[N(O)NO]Na (NOC 18) increased those variables. 3 Similarly, conflicting results have also been reported as regard to the effects of NO in the rostral VLM. 2,4,5 However, all of these studies were performed in anesthetized animals and examined only acute effects of NO or NOS inhibitors. Long-term effects of increased NO production in these regions on the regulation of blood pressure and sympathetic nerve activity in conscious animals remain to be clarified.Replicant-deficient recombinant adenovirus is now widely used for gene transfer into the brain as well as into the blood vessel. 9 -12 Of...

Abstract-Activation of the sympathetic nervous system and renin-angiotensin system has been suggested to contribute to the hypertension caused by chronic nitric oxide synthase inhibition. The aim of the present study was to determine whether angiotensin within the nucleus tractus solitarii (NTS) plays a role in activation of the sympathetic nervous system in this model. Rats were treated with N -nitro-L-arginine methyl ester (L-NAME, 100 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 in drinking water) for 2 weeks. Experiments were performed on anesthetized rats with denervated arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were measured. Microinjection of an angiotensin II type 1 (AT 1 ) receptor antagonist (CV11974) or an angiotensin II type 2 (AT 2 ) receptor antagonist (PD123319) into the depressor region within the NTS (identified by prior injection of L-glutamate) was performed. Microinjection of CV11974, but not of PD123319, produced greater decreases in arterial pressure, heart rate, and RSNA in L-NAME-treated rats than in control rats. The administration of hexamethonium resulted in a larger fall in arterial pressure in L-NAME-treated rats than in control rats. The ACE mRNA level in the brain stem was greater in L-NAME-treated rats than in control rats. These results suggest that increased sympathetic nerve activity plays a role in hypertension caused by chronic nitric oxide synthase inhibition and that activation of the renin-angiotensin system in the NTS is involved at least in part in this increased sympathetic nerve activity via AT 1 receptors. (Hypertension. 2000;36:259-263.) Key Words: nitric oxide Ⅲ sympathetic nervous system Ⅲ brain Ⅲ angiotensin Ⅲ blood pressure Ⅲ heart rate I t is well established that pharmacological inhibition of nitric oxide (NO) synthesis produces acute and chronic hypertension in many animal species, 1,2 but the underlying mechanisms that mediate this hypertension are not fully understood. Although this hypertension was initially attributed solely to the inhibition of endothelial NO synthase (eNOS), numerous studies have demonstrated that the inhibition of neuronal NO may also play a role. [3][4][5][6][7] The administration of an NOS inhibitor, such as N G -monomethyl-Larginine (L-NMMA) or N -nitro-L-arginine methyl ester (L-NAME), into the central nervous system evokes acute increases in both arterial pressure and sympathetic nerve activity. 8,9 These results have been interpreted to suggest that neuronal NO plays roles in the signal transduction pathways involved in the tonic inhibition of sympathetic vasoconstrictor outflow from the brain stem. The removal of this inhibition by NOS inhibitors is postulated to activate the sympathetic nervous system and thereby result in hypertension.Several investigators have demonstrated a great effect of sympathectomy or ganglionic blockade on L-NAME-induced hypertension, suggesting that the sympathetic nervous system is involved primarily in the maintenance, rather than the initiation, of L...

The extent of LVZ is an independent predictor for recurrence even after LVZ homogenization.