Pharmacological study of CB1 receptors modulation in hypertension and possible intrarenal nanoimplants applications

WALTER MANUCHA; DIEGO E. KASSUHA; VIRNA M MARTIN GIMENEZ

Mendoza

Congreso; XXXIV REUNION CIENTIFICA ANUAL DE LA SOCIEDAD DE BIOLOGIA DE CUYO; 2016

Sociedad de Biología de Cuyo

Arterial hypertension is a medical condition considered to be one of the major public health problems in developedcountries. An innovative therapeutic option would involve the use of cannabinoids as activators of type 1 receptors(CB1) in order to cause vasodilation and inhibition of ion absorption at the renal medulla by a nitric oxide (NO)mechanism, resulting in decreased blood pressure. However, cannabinoids have adverse effects in the centralnervous system. In this sense, nanotechnology would allow the controlled release of drugs at specific sites, directingits therapeutic action, and also limiting the occurrence of undesirable effects. Therefore, our objective is to design anintrarenal scaffold of cannabinoid controlled release, comprising polycaprolactone nanofibers obtained by theelectrospinning technique, in order to increase NO bioavailability. It will work with six groups (SHR/WKY control,SHR/WKY sham, and SHR/WKY with nanofibers). Hemodynamic parameters, NO levels, oxygen consumption bythe loop of Henle cells and sodium excretion, will be monitored. We hope to demonstrate that activation of CB1receptors in the renal medulla increases diuresis in hypertensive rats as consequence of increased excretion of NaClby NO-mediated mechanism. In addition, we aspire equally to use nanotechnology to demonstrate its potential toenhance the activity of therapeutic agents while minimizing toxicity and adverse side effects. Thus, intrarenalimplants could be a promising therapeutic alternative for the treatment of hypertension.