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Journal Article 2008; 29(5): 784-789 PubMed PMID: 18987608 Citation  Keywords:  Acetylcholine:metabolism, Animals, Blood Pressure:drug effects, Body Weight:drug effects, Cardiovascular Physiological Phenomena:drug effects, Enzyme Inhibitors:pharmacology, Feedback, Physiological:drug effects, Hypertension:drug therapy, Isometric Contr.   

OBJECTIVES: The effect of 8-week-lasting low-dose treatment of NG-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, was investigated in borderline hypertensive rats (BHR) to examine, whether dose of 1.5 mg/kg/day affects feedback regulation of NO synthesis.

METHODS: Blood pressure (BP) of 12 weeks old Wistar and BHR rats was determined non-invasively by tail-cuff. NO synthase (NOS) activity was determined by conversion of [3H]-L-arginine to [3H]-L-citrulline in the aorta, left ventricle (LV) and hypothalamus. Vascular function of the femoral artery was determined using Mulvany's myograph in isometric conditions.

RESULTS: Chronic low-dose L-NAME treatment of BHR induced sustained blood pressure elevation and left ventricular hypertrophy associated with the decrease in NOS activity in left ventricle and unaltered NOS activity in the aorta. By contrast, the improvement of LV and aortic NOS activity was found in Wistar rats. In hypothalamus, no changes in NOS activity were found in both BHR and Wistar. In Wistar, acetylcholine-induced relaxation of the femoral artery was increased and serotonin-induced and noradrenalin-induced constriction were reduced in L-NAME treated group. These effects, however, were not seen in BHR.

CONCLUSION: The results indicate that NOS/NO feedback regulation works differently under conditions of normotension and prehypertension. Low-dose L-NAME treatment accentuated NO production in normotensive rats, but it failed to improve NOS activity in BHR....

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Journal Article 2004; 25(1-2): 14-23 PubMed PMID: 15159677 Citation  Keywords:  Animals, Cannabinoid Receptor Modulators:physiology, Cannabinoids:pharmacology, Cardiovascular Physiological Phenomena:drug effects, Cardiovascular System:drug effects, Central Nervous System:drug effects, Dronabinol:pharmacology, Humans, Psychotropic Dru.   

: Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the pharmacological effects caused by the use of cannabis, is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several countries. The non-psychotropic cannabidiol (CBD), some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues including spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart. Five endogenous cannabinoids have been detected so far, of whom anandamide and 2-arachidonylglycerol are best characterized. There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of re-uptake into cells and inhibition of their degradation to increase concentration and duration of action. Properties of cannabinoids that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, anti-inflammation, anti-allergic effects, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects....

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