L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

INTRODUCTION: The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. CASE REPORT: A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. DISCUSSION: L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

Hypotensive activity of an n-butanol extract and their purified compounds from leaves of Phyllanthus acidus (L.) Skeels in rats.

We aimed to investigate the effects, identify the active substances and establish the mechanisms involved in the hypotensive activity of an n-butanol extract from leaves of Phyllanthus acidus (PA extract). PA extract caused a decrease in blood pressure of anesthetized rats that was not modified by atropine or propranolol. PA extract caused a persistent dilatation of thoracic aortic rings preconstricted with either phenylephrine or KCl, and these effects were not modified by LNA or removal of the vascular endothelium. For phenylephrine-preconstricted aortic rings, the dilatory activity of the PA extract was not modified by atropine, propranolol or indomethacin. TEA, glybenclamide or ODQ significantly inhibited the dilatory activity of the PA extract on endothelium-denuded aortic rings. Nifedipine or a Ca(2+)-free medium depressed the aortic rings constrictor response to phenylephrine, and that was further augmented by the PA extract. Adenosine, 4-hydroxybenzoic acid, caffeic acid, hypogallic acid, and kaempferol were isolated from the PA extract. Each caused a decrease in blood pressure and dilatation of the aortic rings. LNA or removal of the endothelium reduced this activity. ODQ and TEA attenuated the vasodilatory activity of adenosine whereas glybenclamide and ODQ attenuated the effect of hypogallic acid. These results suggest that the hypotensive activities of the PA extract is likely the result of the direct action of these five compounds on the blood vessels by stimulating release of nitric oxide from the vascular endothelium, in part through stimulation of soluble guanylate cyclase, and opening of K(ATP) and K(Ca) channels in the vascular smooth muscle.

Pharmacological mechanisms underlying the vascular activities of Loranthus ferrugineus Roxb. in rat thoracic aorta.

AIM OF THE STUDY: The present study was aimed to investigate the pharmacological basis for the use of Loranthus ferrugineus in hypertension. MATERIALS AND METHODS: Loranthus ferrugineus methanol extract (LFME) was obtained using Soxhelt extractor and then successively fractionated using chloroform, ethyl acetate and n-butanol. The n-butanol fraction of LFME (NBF-LFME) was studied using isolated rat thoracic aorta. RESULTS: NBF-LFME (1.0 x 10(-5) to 3.0mg/ml) was found to be the most potent to concentration-dependently relax the endothelium-intact phenyephrine (PE, 1 microM)- and high K(+) (80 mM)-precontracted rat aortic rings. Removal of the endothelium completely abolished the vascular relaxing properties of NBF-LFME. Pretreatment with atropine (1 microM), L-NAME (10 microM), indomethacin (10 microM) and methylene blue (10 microM) significantly blocked NBF-LFME-mediated relaxation. Endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were significantly enhanced in aortic rings pretreated with NBF-LFME when compared to those observed in control aortic rings. On the contrary, glibenclamide (10 microM), propranolol (1 microM) and prazosin (0.01 microM) did not alter NBF-LFME-induced relaxation. CONCLUSIONS: The results suggest that NBF-LFME induced vascular relaxation by stimulating muscarinic receptors, activating the endothelium-derived nitric oxide-cGMP-relaxant pathway, promoting prostacyclin release and/or possibly through its ability to lengthen the released nitric oxide half-life. The present data further supports previous in vivo findings and explain the traditional use of Loranthus ferrugineus as an anti-hypertensive agent.

Angiotensin-(1-7) inhibits the angiotensin II-enhanced norepinephrine release in coarcted hypertensive rats.

Since it has been suggested that angiotensin (Ang) (1-7) functions as an antihypertensive peptide, we studied its effect on the Ang II-enhanced norepinephrine (NE) release evoked by K+ in hypothalami isolated from aortic coarcted hypertensive (CH) rats. The endogenous NE stores were labeled by incubation of the tissues with 3H-NE during 30 min, and after 90 min of washing, they were incubated in Krebs solution containing 25 mM KCl in the absence or presence of the peptides. Ang-(1-7) not only diminished the K+-evoked NE release from hypothalami of CH rats, but also blocked the Ang II-enhanced NE release induced by K+. Ang-(1-7) blocking action on the Ang II response was prevented by [D-Ala7]Ang-(1-7), an Ang-(1-7) specific antagonist, by PD 123319, an AT2-receptor antagonist, and by Hoe 140, a B2 receptor antagonist. Ang-(1-7) inhibitory effect on the Ang II facilitatory effect on K+-stimulated NE release disappeared in the presence of Nomega-nitro-L-arginine methylester and was restored by L-arginine. Our present results suggest that Ang-(1-7) may contribute to blood pressure regulation by blocking Ang II actions on NE release at the central level. This inhibitory effect is a nitric oxide-mediated mechanism involving AT2 receptors and/or Ang-(1-7) specific receptors and local bradykinin generation.

[The treatability of refractory or resistant hypertension by personalized antihypertensive chronotherapy based on ambulatory monitoring of the arterial pressure]. / Trattabilità dell'ipertensione ribelle o resistente mediante cronoterapia antipertensiva personalizzata basata sul monitoraggio ambulatorio della pressione arteriosa.

The present paper is aimed at detecting whether the combination of ambulatory blood pressure monitoring (ABPM) and antihypertensive chronotherapy can be usefully exploited in the treatment of hypertension which appears to be rebel or resistant to pharmacological administration. The study was carried out in 28 hypertensive patients (15 men and 13 women, 45 +/- 10 years old), rebel (10 cases) or resistant (8 cases) to a conventional antihypertensive therapy. The ABPM was performed weekly in order to see when the eventual patient was cured by the therapy which was synchronized to the "relative hypertensive peak" of the antimeridian, postmeridian and nocturnal part of the day. The actuarial analysis documented that at the end of the sixth week no case remained rebel or resistant to the antihypertensive chronotherapy, suggesting that the combination of the ABPM with the chronotherapeutical treatment is highly recommended in presence of apparently refractory cases of hypertension.