Effect of an avocado oil-rich diet over an angiotensin II-induced blood pressure response.

We studied the effect of an avocado oil-rich diet on (1) the blood pressure response to angiotensin II (AngII) and (2) the fatty acid composition of cardiac and renal membranes on male Wistar rats. The avocado oil-rich diet induced a slightly higher AngII-induced blood pressure response in the rats as compared to the control rats. In cardiac microsomes, avocado oil induced an increase in oleic acid content (13.18+/-0.33% versus 15.46+/-0.59%), while in renal microsomes, the oil decreased alpha-linolenic acid content (0.34+/-0.02% versus 0.16+/-0.12%), but increased the arachidonic acid proportion (24.02+/-0.54% versus 26.25+/-0.54%), compared to control. In conclusion, avocado oil-rich diet modifies the fatty acid content in cardiac and renal membranes in a tissue-specific manner. The rise in renal arachidonic acid suggests that diet content can be a key factor in vascular responses.

Vasodilator activity of the aqueous extract of Viscum album.

The aqueous extract of Viscum album leaves showed a significant coronary vasodilator activity on the Langendorff's isolated and perfused heart model. The data obtained suggest that the aqueous extract of V. album contains some biologically active principles that may act as inducers of the nitric oxide/soluble guanylate cyclase pathway.

Flow stimulates nitric oxide release in guinea pig heart: role of stretch-activated ion channels.

Blood flow regulates vessel tone triggering the release of nitric oxide; however, the mechanism involved in this phenomenon is unknown. We investigated whether coronary flow induces nitric oxide release in the isolated perfused guinea pig heart and the role of the stretch-activated ion channels in the effect of flow. We used gadolinium (3 microM) in order to block these channels, and estimated nitric oxide release by an oxyhemoglobin method. The results have shown a flow-dependent stimulation of nitric oxide release (fivefold increase at perfusion flow of 25 ml/min). Gadolinium inhibited this effect in a dose-dependent fashion. Acetylcholine was able to stimulate nitric oxide release in presence of gadolinium. We concluded that coronary flow stimulates nitric oxide release in the guinea pig heart. Stretch-activated ion channels mediate this effect. Acetylcholine and flow stimulate nitric oxide release by different mechanisms of action.

[The influence of coronary flow on atrio-ventricular transmission and ventricular contraction in the isolated guinea pig heart]. / Influencia del flujo coronario sobre la conducción auriculoventricular y la contracción ventricular en corazón aislado de cobayo.

UNLABELLED: It has been demonstrated that coronary flow, through hemodynamic forces, stimulates ventricular contraction and atrio-ventricular transmission; however, the mechanisms involved in these effects remain unknown. A possibility to explain the transduction mechanism, from a mechanical stimulus into a physiological response, could be the stretch-activated ion channels. Additionally we explored the role of nitric oxide as mediator of these actions. METHODS: We used the isolated perfused guinea pig heart according to the method of Langendorff, perfused with Krebs solution. We recorded the ventricular contraction by development of left ventricular pressure and the atrio-ventricular transmission. We studied the effects of the stretch activated ion channel blocker; gadolinium. Synthesis of nitric oxide was inhibited by L-NAME and induced with L-arginine. RESULTS: Gadolinium inhibited the stimulating effect of flow on atrio-ventricular transmission and ventricular contraction. Verapamil, a specific blocker of calcium channels, had no effect in the stimulatory effect of flow indicating that this type of calcium channel, do not play significant role in the effects of flow. L-NAME and L-arginine did not have effects on the effects of flow. CONCLUSION: The stimulating effect of coronary flow in these parameters is regulated by stretch-activated ionic channels. This effect is independent of nitric oxide.

[Myocardial ischemia detection with adenosine administration and SPECT. Initial experience in Mexico]. / Detección de isquemia miocárdica mediante la administración de adenosina y técnica SPECT. Experiencia inicial en México.

UNLABELLED: Myocardial perfusion SPECT has a high sensitivity for the diagnosis of myocardial ischemia. Adenosine has been recently used to induce myocardial ischemia in the United States and Europe. At the present time there is not published experience using adenosine in Mexico. METHOD: We studied 22 patients with suspected myocardial ischemia. Coronary angiography was performed in 17 patients. We used a 8 mCi rest Tc-99m sestamibi followed by a 6 minute infusion of adenosine at a dose of 140 ug/kg/min; 24 mCi of Tc-99m were injected after the third minute of adenosine infusion. Patients returned 2 or 3 days later for a new stress study using physical stress or dipiridamole and the images were read using a 20 segments analysis and each segment was scored using a 5 points scale (0 = normal to 4 = absent uptake). The results were then compared with the adenosine images. RESULTS: The segmental score agreement between adenosine and physical or dipyridamole stress were good with 90% exact correlation. The side effects experienced by patients who received dipyridamole and adenosine were similar. CONCLUSION: Adenosine is a good alternative to induce myocardial ischemia. It showed a good correlation with physical or dipyridamole stress test.

[The role of adenosine on the anti-arrhythmic action of digitalis glycosides]. / Papel de la adenosina sobre la acción antiarrítmica de los digitálicos.

UNLABELLED: The action of adenosine on atrial functional refractory period, as well as on its ability to interrupt atrial flutter is similar to that of digitalis. The latter suggests the possible existence of an adenilic component to digitalis action. To test this possibility, we measured the plasma concentrations of adenosine after ouabain infusion in dogs, and we investigated the effect of digitalis on atrial refractory period and on flutter in conditions of cholinergic inhibition and purinergic blockade. Ouabain was administered until ventricular fibrillation was induced. Blood was obtained from both the coronary sinus and the femoral vein, and adenosine was measured by liquid chromatography. The refractory period was measured by applying an extra stimulus at variable intervals following a train of 10 basic beats. Flutter was induced by stimulation of the posterior internodal pathway. RESULTS: The concentration of adenosine in plasma collected from the coronary sinus increased by more than 100%; the effect of digitalis on atrial refractory period was independent of cholinergic blockade, but it was inhibited by aminophylline; the ability of digitalis to interrupt flutter was modified by aminophylline. CONCLUSION: The antiarrhythmic action of digitalis seems to include an adenilic component, that results from the liberation of adenosine in the heart.

Characterization of 3-nitropropionic acid-induced bradycardia in isolated atria.

3-Nitropropionic acid (3-NPA) was identified as the toxic component of several plants and fungi. Recently, it was described that 3-NPA produced hypotension, accompanied by a paradoxical bradycardia. In this study, we identified a possible mechanism of action, explaining the effect of 3-NPA on cardiac tissue. We used isolated, spontaneously beating atria and heart mitochondria to measure electrophysiological properties and mitochondrial oxygen consumption. We also measured Na+/K+ ATPase activity and intracellular ATP levels. In isolated spontaneously beating atria, 3-NPA (10(-4) M) decreased heart rate by 62 +/- 3%. This agent did not affect the amplitude or duration of action potentials. The duration of intervals between two action potentials, however, was prolonged from 530 +/- 285 to 1400 +/- 600 ms after 3-NPA exposure (10(-2) M). Oxygen consumption by heart mitochondria was inhibited by 3-NPA when either malate/glutamate or succinate were used as metabolism substrates. Cytochrome C oxidase activity was not affected by 3-NPA. Finally, atrial ATP content decreased 65 +/- 3% after 3-NPA treatment. In conclusion, we show that 3-NPA decreases atrial rate by increasing the action potential phase 4, probably by inhibition of mitochondrial respiration, thereby decreasing cardiac ATP content. This suggests that 3-NPA-induced bradycardia may be related to intracellular ATP depletion.

Action of adenine derivatives on experimental atrial flutter in the canine heart.

We have studied the effects of adenosine (Ado) and adenosine derivatives on an experimental atrial flutter (AFL) in the canine heart. Moreover, we have assessed these adenine derivatives on some electrophysiological parameters (the conduction time and functional refractory period) of the posterior internodal pathway (PIP) and of the ordinary atrial myocardium (OAM). The adenosine derivatives assessed were adenosine 5'-monophosphate (AMP), adenosine 3' 5'-monophosphate (cAMP) and adenosine 5'-triphosphate (ATP). Ado, AMP, and cAMP transformed the atrial flutter into a short episode of atrial fibrillation that terminated spontaneously to sinus rhythm. This effect was prevented by previous blockade of A1 purinergic receptors with aminophylline, but not by parasympathectomy (vagotomy and atropine). ATP also suppressed the AFL, but in this case, sinus rhythm was achieved without an intermediate episode of atrial fibrillation, and the effect of ATP was not prevented by A1 purinergic blockade. Ado, AMP and cAMP extended the functional refractory period measured in the PIP, but reduced this parameter in the OAM (p < 0.01). The different response of atrial tissues to the adenosine and its monophosphate derivatives was not elicited by ATP. This derivative caused a prolongation of FRP on both atrial tissues PIP and OAM (p < 0.05). The changes produced by Ado and its monophosphate derivatives on FRP was blocked by aminophylline. The effect of adenine derivatives on AFL may be explained by the dispersion of refractoriness created as a result of the heterogeneous response of atrial tissues to these agents. Our results support the hypothesis of an agonistic action of adenine derivatives on atrial purinergic receptors.

The effect of ovariectomy on depressed contractions to phenylephrine and KCl and increased relaxation to acetylcholine in isolated aortic rings of female compared to male rabbits.

1. Differences in vascular responses to phenylephrine, acetylcholine (ACh) and potassium chloride (KCl) were studied in rabbit aorta from female and male rabbits, in the absence and presence of an inhibitor of nitric oxide (NO) production, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). 2. Phenylephrine and KCl-induced contractions, were significantly reduced in amplitude (P < 0.01) in the rings from female rabbits compared to those from male rabbits. 3. ACh-induced relaxation was greater (P < 0.01) in aortic rings from females than from males. 4. Incubation of the rings with L-NAME abolished the phenylephrine-induced contraction differences between rings from male and female rabbits. 5. Ovariectomy eliminated the differences in vascular responses to phenylephrine, KCl and ACh of aortic rings from the female rabbits. 6. Both basal and ACh-stimulated release of nitrites from aortic rings was greater (P < 0.01) in vascular tissue from female than male rabbits. 7. These results indicate that differences in vascular reactivity in aortic rings from male and female rabbits may be associated with a higher release of NO, resulting in an increased vasodilator response in the female rabbits.

[The effects of digitalis compounds on K(+)-induced relaxation in aortic rings]. / Efectos de los compuestos digitálicos sobre la relajación inducida por K+ en anillos de aorta.

It has been shown that, changes in the structure of the cardiac glycoside, are related to changes in their biological effects. In the present study we compared the effects of two structurally different digitalis compound (ouabain and ouabagenin), on K+ induced vascular relaxation as an index of the Na+K+ ATPase activity. Ouabain was the most potent compound tested, and had vasoconstrictor effect on the rat aortic rings, as, well as inhibitory effect on the K(+)-induced relaxation. Ouabagenin did not affect either the vascular tone or K(+)-induced relaxation. It is well known that changes in the part of the structure of the cardiac glycoside that contain the sugar, are important to maintain some of their biological effects. In this paper we demonstrate that elimination of the 1-rhamnose in ouabagenin reduces its vascular effects associated to the inhibition of the Na+ K+ ATPase pump.

[Changes in the vasoconstrictor action of noradrenaline and in its receptor-binding kinetics induced by sex hormones]. / Cambios en la acción vasoconstrictora de la noradrenalina y en su cinética de unión a receptores, inducidos por hormonas sexuales.

The role of testosterone/17 B estradiol ratios (T/E), on the vasoconstrictor effect of norepinephrine (NE), were studied in strips of carotid arteries from dogs. T/E of 0.1 (T = 1 nM/E = 10 nM) shifted the concentration/effect (C-E) curve of NE to the right. T/E of 10 (T = 10 nM/E = 1 nM) deviated it to the left. T (1 nM and 10 nM) shifted the C-E curve of NE to the right; E = 1 nM did not modify it; E = 10 nM, shifted it to the left. In microsomal fraction of carotid arteries, adrenergic receptors were characterized with 3H-NE binding, and the role of T/E ratios also studied. Under the influence of T/E ratio of 10, the agonist affinity (Ka), was increased from 100 nM-1 to 128 nM-1, the receptors density (Bmax), increased from 78.3 nM to 148 nM. E (1 nM) reduced Ka to 88 nM-1, T did not change any of these parameters. In conclusion, T/E ratios of 10, as in male, may enhance the vasoconstrictor activity of NE, increasing Ka and Bmax of adrenergic receptors.

[Effects of the polyamines putrescine, spermidine and spermine on the hypertensive action of norepinephrine in anesthetized dogs]. / Efecto potenciador de las poliaminas putrescina, espermidina y espermina sobre la accion presora de la noradrenalina en el perro anestesiado.

In anesthetized and vagotomized dogs, we investigate the associative effects on blood pressure of norepinephrine (NE) with the three polyamines putrescine (Pt), spermidine (Sd) and spermine (Se). Experimental series were performed under beta adrenergic blockade (propranolol 0.5 mg/Kg, iv.), alpha adrenergic blockade (phenoxybenzamine 15 mg/Kg, iv.), and under calcium antagonistic action (verapamil 0.3 mg/Kg, iv.). The three polyamines induced a potentiation on the hypertensive effect of NE, they change the dose/response curve to the left side in a potency rank of Se greater than Sd greater than Pt. Such potentiation was not different when a beta adrenergic blockade or calcium antagonism was present; however phenoxybenzamine neutralized it. On the other side, polyamines had a hypotensive effect when were administered alone to the animals. Such effect is related to a histamine releasing properties of the polyamines, and was abolished by previous administration of anihistaminic agents chlorpheniramine (5 mg/kg, iv.) and cimetidine (20 mg/Kg, iv.). In conclusion our results indicate that the potentiation of the hypertensive effect of NE by polyamines, could be attained through a mechanism which involves the alpha adrenergic receptors of the vascular smooth muscle but is not related to the calcium channels that show voltage dependence.

[Pharmacologic study of dopamine catabolites on the contractility of isolated guinea pig myocardium]. / Estudio farmacológico de catabolitos de dopamina sobre la contractilidad del miocardio aislado de cobayo.

Tetrahydroisoquinolines (TIQs) are alkaloids originated as natural catabolic derivatives of catecholamines (CAT). Dopamine, under special circumstances, condenses with aldehydes to produce tetrahydropapaveroline (THP), salsolinol (SOL) and salsoline (SAL). We investigated the inotropic activity of THP, SOL and SAL on the isometric contractility of papillary muscles isolated from guinea pigs hearts and compared their actions to those corresponding to adrenaline (A) and isopropylarterenol (ISO). In order to analyze their combined effects, TIQs and A were applied simultaneously. THP, SOL and SAL produced positive inotropic effects as beta receptor agonists; their actions were antagonized with propranolol. The inotropic efficacy of TIQs compared to that of catecholamines, is: CAT = 1; SAL = 0.32; THP = 0.47 and SOL = 0.32. Their middle effective dose (DE50), indicates an order of potency of: ISO = SAL greater than A = THP greater than SOL. Combination of THP or ISO with A produces an additive effect; however, SAL behaves as a partial agonist, meaning that it produces an antagonistic, non-competitive type effect on the inotropic action of adrenaline. Chemical structure of TIQs shows significant relationship with their pharmacological activity on ventricular myocardium, similar to that of catecholamines. The influence of the methoxyl group attached to C-7 in SAL, as the only difference with SOL which instead has a hydroxyl group in that position, deserves special mention; such structural difference provides to SAL bigger inotropic efficacy and potency, as well as beta adrenergic antagonistic activity. The results of the present paper emphasize the biological significance of active catabolites from catecholamines as are the tetrahydroisoquinoline compounds.

[Effect of adenosine on P50 and its relation to 2,3-diphosphoglycerate]. / Efecto de la adenosina sobre la P50 y su relación con el 2,3-difosfoglicerato.

The effects of increasing doses of intravenous adenosine upon the dissociation haemoglobin curve (DHC) and its relation to the intraerythrocytic level of 2,3-diphosphoglyceric acid (2,3-DPG), were studied in 17 anesthetized dogs. The DHC moved significantly to the left in all dogs except at the dose of 120 micrograms/kg/min which induces a displacement to the right. These changes in the DHC were parallel to the intraerythrocytic levels of 2,3-DPG. We conclude that adenosine modifies the DHC, shifting it generally to the left, and that this effect seems to be related to a change in the intraerythrocytic level of 2,3-DPG.

[Diagnosis of ischemic heart disease by infusion of isopropylarterenol: comparison with ergometry and validation by coronary arteriography]. / Diagnóstico de la cardiopatía isquémica con infusión de isopropilarterenol: comparación con ergometría y validación mediante coronariografía.

In order to evaluate isopropylarterenol infusion (ISO) as a diagnostic procedure in ischemic heart disease, we performed a clinical study in 54 patients controlled with exercise stress test (ERGO) and validated by coronary arteriography. Eighteen patients had normal coronary arteriographic findings and 36 had coronary artery disease. In both groups the hemodynamic response was similar in either test used (ERGO or ISO), when similar heart rates were reached. The sensitivity of ERGO was 80.55% and 86.11% for ISO and specificity of 77.72% and 72.26% respectively in the diagnosis of coronary artery disease. When both tests are associated their sensitivity is 83.30% and their specificity is 75.0% (Table V). The ISO test was not accompanied with adverse effects and could be considered as a useful method in the diagnosis of coronary heart disease, similar to ERGO. Additionally ISO could be applied to understand some physiopathological mechanisms of ischemic heart disease.

[Demonstration of the role of stimulation of purinergic receptors in the electrophysiologic effect of adenylic compounds in man]. / Demostración del papel de la estimulación de receptores purinérgicos en el efecto electrofisiológico de los compuestos adenílicos en el hombre.

In order to study the mechanism of action of AMP on the AV node conduction, 10 patients with re-entrant tachycardia including the AV node in the circuit (SVT) were studied. The mean age was 32.8 +/- 11.1. Tachycardia was induced by programmed atrial stimulation. Electrophysiological studies were made in all the cases. Intravenous injection of AMP suppressed SVT in all the patients in the first part of the study. The mean doses was 0.095 +/- 0.037 mg/Kg., and the mean time was 15.2 +/- 2.6 sec. In the second part (after 0.04 mg/Kg. IV atropine) the induced SVT was suppressed with a mean doses of 0.122 +/- 0.45 mg/Kg of AMP (P = NSD) in a mean time of 16.2 +/- 2.2 sec. (p = NSD). In the last part of this study the intravenous injection of aminophylline (4 mg/Kg) avoided the suppression of induced SV T in 8/10 patients. In to patients the AMP doses was 0.250 mg/Kg., and in the other 0.075 mg/Kg. Our studies demonstrated that the mechanism of action of AMP is by means of agonistic stimulation of purinergic receptors in the AV node.

Effect of pertussis toxin on the heart muscarinic-cholinergic receptors and their function.

Administration of pertussis toxin to rats induced a significant increase in heart rate that was evident as soon as 24 hours after the administration of the toxin and that persisted for at least 15 days. Electrical stimulation of the vagus decreased dramatically the heart rate of control animals but was unable to do it so in rats treated with pertussis toxin. In cardiac membranes muscarinic agonists decreased adenylate cyclase activity (approximately equal to 20-25%); no effect was observed in membranes obtained from toxin-treated animals. Agonist displacement of antagonist binding [( 3H] Quinuclidinyl benzilate) indicated that treatment with pertussis toxin decreased the proportion of receptors in the high affinity state for agonists. All these data suggest that blockade of the parasympathetic tone plays a key role in the induction of tachycardia by pertussis toxin.