Striatal Protection in nNOS Knock-Out Mice After Quinolinic Acid-Induced Oxidative Damage.

Under pathological conditions, nitric oxide can become a mediator of oxidative cellular damage, generating an unbalance between oxidant and antioxidant systems. The participation of neuronal nitric oxide synthase (nNOS) in the neurodegeneration mechanism has been reported; the activation of N-methyl-D-aspartate (NMDA) receptors by agonist quinolinic acid (QUIN) triggers an increase in nNOS function and promotes oxidative stress. The aim of the present work was to elucidate the participation of nNOS in QUIN-induced oxidative stress in knock-out mice (nNOS-/-). To do so, we microinjected saline solution or QUIN in the striatum of wild-type (nNOS +/+), heterozygote (nNOS+/-), and knock-out (nNOS-/-) mice, and measured circling behavior, GABA content levels, oxidative stress, and NOS expression and activity. We found that the absence of nNOS provides a protection against striatal oxidative damage induced by QUIN, resulting in decreased circling behavior, oxidative stress, and a partial protection reflected in GABA depletion. We have shown that nNOS-derived NO is involved in neurological damage induced by oxidative stress in a QUIN-excitotoxic model.

[Effect of alpha, beta blocker, labetol on the angiotensin renin system in arterial hypertension]. / Efecto del bloqueador alfa y beta, labetalol sobre el sistema renina angiotensina en la hipertensión arterial.

The effect of labetalol, a new alpha and beta adrenergic blocker, on blood pressure, heart rate, plasma renin activity (PRA), and urinary aldosterone excretion was assessed in 23 essential hypertensive patients, divided in 2 subgroups: 11 with normal electrocardiogram and 12 with left ventricular hypertrophy (LVH). In the first subgroup significant differences were found in the arithmethyc mean for sistolic blood pressure in sitting position (control: 166.1 +/- 17.2 mm of Hg treatment: 153.9 +/- 13.8, p less than or equal to 0.005) and in standing position (control: 165.3 +/- 17.3, treatment: 152.8 +/- 13.8, p less than or equal to 0.005) and for diastolic blood pressure (control: 102.7 +/- 12.6 to 89.9 +/- 10.1, p less than or equal to 0.001 and 103.2 +/- 11.8 to 91.2 +/- 10.8, p less than or equal to 0.001; in sitting and orthostatic positions, respectively.). No significant differences were found in the group with LVH. Heart rate decreased in the total population during treatment (- 6.0 +/- 7.5, p less than or equal to 0.05 and - 5.4 +/- 7.5 beats per minute, p less than or equal to 0.05 in sitting and orthostatic positions, respectively. PRA diminished in 12 of 15 cases studied (- 2.5 +/- 4.65 ng/ml/hr., p greater than 0.5). Correlation coefficient between decrements of diastolic blood pressure (sitting position) and ARP was 0.637. Aldosterone decreased in a non significant way during treatment. These data support the thesis of an important role of the adrenergic system in the pathogenesis of non complicated essential hypertension and, therefore, simultaneous alpha and beta receptor blockade in these cases has a better therapeutic effect. The good correlation between the decrements of ARP and blood pressure suggests an intervention of the inhibition of renin angiotensine system, brought about by the blocker property of labetalol, in the antihypertensive mechanism of the drug.

[Further cases of Ehlers-Danlos syndrome of the renovascular dysplasic variety]. / Nuevas observaciones del sindrome de Ehlers-Danlos de la variedad displáscia renovascular

One hundred and twenty patients with arterial hypertension and 3 cases of fibromuscular displasia of the renal arteries (FDRA) (group D) were studied; besides the usual arterial hypertension work up, a search of Ehlers-Danlos syndrome stigmata was carried out in all patients. The population of 120 hypertensive patients were classified in 3 groups: group A, fromed by 104 subjects without EDS stigmata; group B, constitued by 7 cases with hypermobility of one to three metar-carpophalangic joints and group C in which 9 subjects with hipermobility of more than 3 metacarpophalangic joints were included. Neither case of groups A and B showed arteriographic signs of FDRA. In 4 cases of group C there were arteriographic evidence of FDRA (3.3% of the whole population) and stigmata of SED (2 cases with skin biopsy positive for this entity). Two cases of group D showed stigmata of SED and a positive skin biopsy; the other case had a normal histology of skin and no clinical signs of SED. The presence of SED stigmata in a patient with arterial hypertension should alert the clinician in the diagnosis of FRDA; in such a case it is recommended that a renal arteriography be performed. In this paper similarities of SED of the arterial type and some cases of FDRA are remarked and it is proposed the both entities share the same or a very closed molecular collagen defect.