Chronic nicotine administration. Analysis of the development of hypertension and glutamatergic neurotransmission.
Among numerous neurotransmitters involved in central cardiovascular control, glutamate is one of the most studied transmitters that are related to nicotine considering its release and its postsynaptic regulation. However, there are no conclusive studies about nicotine effects on glutamatergic system and its relevance on hypertension development, which can help to understand the role of these two systems in that pathology. In this context, the objective of the present study is to evaluate the effects of systemic chronic nicotine exposure on hypertension development as well as the interaction between nicotine and the glutamatergic system in normotensive and neurogenic hypertensive rats. By means of high performance liquid chromatograph, immunohistochemistry, in situ hybridization and binding techniques, glutamatergic system was evaluated in SHR and Wistar Kyoto (WKY) rats treated with nicotine, delivered subcutaneously through nicotine pellets, for 8 weeks. The most important findings in this study were that (1) moderate doses of nicotine accelerated the onset and increased blood pressure in SHR but not in WKY rats, (2) the nicotine dosage and time of treatment employed did not affect body weight, (3) chronic nicotine treatment differentially affected glutamatergic system in normotensive and hypertensive rats, and (4) spontaneously hypertensive rats seem to be more sensitive to peripherally administered nicotine than Wistar Kyoto rats considering blood pressure and glutamatergic neurotransmission changes. In conclusion, we have demonstrated that a moderate dose of nicotine accelerates the onset and exacerbates hypertension in the SHR and that might be, at least in part, related to the modulation of glutamatergic neurotransmission.
Ferrari
Merari F R
MF
Department of Physiology, Institute of Biosciences, University of São Paulo, Rua do Matão, Travessa 14, n.321, Cidade Universitária-São Paulo, SP 05508-090, Brazil.
Fior-Chadi
Debora R
DR
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003164:Competitive Bidding / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D018690:Excitatory Amino Acid Agonists; D018722:Nicotinic Agonists; D018698:Glutamic Acid; D009538:Nicotine