Central hypotensive action of clonidine requires nitric oxide.

Background- Clonidine has an antihypertensive effect by its action in the brain and, because we observed that the tonic production of nitric oxide (NO) in the brain is required to maintain blood pressure at its low, normotensive level, the current study was designed to determine whether the hypotensive action of clonidine resulted from its stimulation of excess NO in the brain. Methods and Results- Porphyritic microsensors were used to quantify NO concentration in the nucleus tractus solitarius (NTS) in vitro in brain slices and in vivo in the anesthetized rat. In both preparations, the basal production of NO in the NTS was 15+/-3 nmol/L. In vitro stimulation of the NTS with clonidine (50 nmol/L) resulted in an increase in the NO concentration to 84+/-7 nmol/L. In vivo, the intracerebroventricular (ICV) infusion of clonidine (0.03 microgram) caused an increase in NO concentration in the NTS to 128+/-17 nmol/L. This ICV injection of clonidine caused a fall in mean arterial pressure of -22+/-1 mm Hg and a decrease of heart rate of -18+/-2%. The blockade of NO production with N(G)-nitro-L-arginine-methyl ester (2 micromol; delivered ICV, 30 minutes before the clonidine) reduced responses to clonidine for both mean arterial pressure and heart rate (-3+/-1 mm Hg and -2+/-1% change, respectively). Conclusion- The stimulation of the release of NO in the brain by clonidine contributes to its central antihypertensive action.

Central depressor action of nitric oxide is deficient in genetic hypertension.

Inhibition of NO synthase (NOS) in the central nervous system (CNS) causes a pressor response. This observation indicates that NO is normally produced at CNS site(s) where it has a tonic blood pressure lowering effect. The current study tests the hypothesis that a deficient NOS activity in the CNS may contribute to the pressure elevation in genetically hypertensive rats. NO administered intracerebroventricularly (ICV) caused a greater fall in mean arterial pressure (MAP; femoral artery) in hypertensive (SHRSP) than in normotensive (WKY) rats, -66.1 +/- 3.4 mm Hg v -23.7 +/- 3.9 mm Hg, respectively. Yet when endogenous NO was increased by stimulating NOS with ICV calcium, the depressor response was less in SHRSP than in WKY, 13.7 +/- 1.1 mm Hg v 26.7 +/- 1.9 mm Hg. Likewise, when NOS was blocked with N omega- nitro-L-arginine methyl ester (L-NAME), the resultant pressor response was less in SHRSP than in WKY, 13.8 +/- 1.1 mm Hg v 22.2 +/- 1.1 mm Hg. Blockade of the action of cGMP, a mediator of the action of NO, caused a pressor response of 6.0 +/- 2.8 mm Hg and 22.6 +/- 8.7 mm Hg (P < .01) in the hypertensive and normotensive rats, respectively. Electrolytic ablation of the anteroventral third cerebral ventricle (AV3V) did not alter blood pressure responses to NO or to agents that alter NOS activity. We conclude that a deficit in NOS activity in some other central cardiovascular regulatory area may contribute to the elevated arterial pressure of these genetically hypertensive rats.

Antalarmin blockade of corticotropin releasing hormone-induced hypertension in rats.

Central administration of CRH results in endocrinological, cardiovascular, and behavioral effects that suggest stress or anxiety. Among these is a marked pressor response. Parenteral administration of CRH, however, results in hypotension. We used parenteral administration of antalarmin, a novel, small molecule CRH1 receptor antagonist, and alpha-helical CRH(9-41), a peptidic CRHR1/CRHR2 antagonist to attempt to determine the receptor mechanisms through which CRH is acting in both of these situations. Our results suggest that the hypertension produced by central CRH administration is mediated through central CRHR1 receptors, whereas the hypotension produced by parenteral CRH administration is mediated through peripheral CRHR2 receptors.

[Value of combined electro- and vectorcardiography in the estimation of left ventricular mass in the elderly]. / Valor del electro y vectorcardiograma combinados en la estimación de la masa ventricular izquierda en la tercera edad.

Electro- and vectorcardiographic methods describe left ventricle increases only when it has attained a significantly high magnitude, but even in such circumstances the exactitude of such methods is substantially lower than that of echocardiogram (ECHO). On the other hand, in comparison to other age groups, there have been relatively few reports relating electrocardiogram (ECG), vectorcardiogram (VCG) and ECHO with left ventricular mass (LVM) in healthy elderly subjects where increases of the left ventricle mass, if present, would be small or moderate. In this paper LVM as well as LVM index (iLVM) from a group of healthy subjects belonging to a physical training program for elderly, was studied by means of ECHO and computerized ECG and VCG. From ECG, voltage indexes and other LVM associated parameters were extracted; from VCG, planar maximum vectors, areas within VCG loops and maximal spatial magnitude of QRS (SM), were measured. Results of LVM (221 +/- 37.9, g) were higher than figures reported for others groups. Voltage indexes showed normal values, but QRS duration was somewhat prolonged. The best simple linear regression, combining variables from VCG and ECG was maximum horizontal vector (Vmax-Hor) vs Sokolow-Lyon index (SOK) and combining ECHO with ECG or VCG, LVM vs Area inside horizontal loop (AreaHor). A model for estimation of LVM from electrical variables was obtained by multiple linear regression; combining five variables from ECG and VCG. The best model included Sokolow-Lyon index and variables from horizontal and sagittal planes of VCG and spatial magnitude of QRS: LVM = 4.8 SOK-186 VmaxHOR-80 VmaxSAG + 126SM + 340 AreaH + 175.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraocular pressure measurement in the conscious rat.

PURPOSE: To develop a method for measurement of intraocular pressure in conscious, unsedated rats. METHODS. The animal was gently held with a thick fabric mitten, topical anesthetic drops were instilled and the Tono-Pen was applied to the cornea. RESULT: Measurements in a total of 51 animals did not differ significantly among four strains studied: the overall mean intraocular pressure+/-standard deviation was 13.0+/-1.2 mm Hg. Several intraocular pressure tolerance limits were calculated from this conscious rat data to provide a baseline estimate for future studies. CONCLUSIONS: This measurement method in conscious rats may contribute to making this widely used laboratory animal available for intraocular pressure research.