Hypertension and vascular remodeling: beneficial effects of chronic treatment with C-type natriuretic peptide

COSTA MARÍA DE LOS ÁNGELES; SUEIRO LAURA; MUÑOZ FLORENCIA; BOUCHET GONZALO; ROMERO MARIANA; CERNIELLO MICAELA; REYES ANA; BARRIONUEVO EMILIANO; TOBLLI JORGE; CANIFFI CAROLINA

Atenas

Congreso; Meeting ESH - ISH Hypertension 2014; 2014

European Society of Hypertension - International Society of Hypertension

Objective: C -type natriuretic peptide ( CNP ) and nitric oxide (NO) have effects on the endothelium and the vascular smooth muscle to be two major factors involved in the regulation of blood pressure and cardiovascular homeostasis. Previous studies showed that acute infusion of CNP induces an increase in the activity of the endothelial isoform of NO synthase (NOS) in vascular normotensive and spontaneously hypertensive rats (SHR ) . The aim was to evaluate the effects of chronic administration of CNP on NO system and vascular morphology in SHR. Design and Methods : Male Wistar normotensive rats ( W ) and SHR 12 weeks of age received infusion of CNP ( 0.75 mg / hour) or saline (S , NaCl 0.9% w / v ) by subcutaneous osmotic pumps ( Alzet ) for 14 days getting four experimental groups: SF - W , W -CNP , SHR and SHR -SF -CNP . After treatment , systolic blood pressure was measured by tail- cuff method (SBP, mmHg). Subsequently the animals were sacrificed by decapitation and the aorta was extracted to determine the activity of NOS (pmol [ U14C ] L -citrulline / g tejido.min ) using [ U14C ] L -arginine as a substrate. Also the thickness of the middle layer ( um) , and its relation to the diameter (micron ) lumen ( medium / lumen) on sections stained with hematoxylin - eosin was evaluated elastin density (number of fibers / thickness , um -1 ) by Verhoeff ´s stain - Van Gieson , signs of vascular fibrosis by picrosirius red ( stained area / total area ) and the expression of TGF- β by immunohistochemistry ( stained area / total area , % ) and the expression by immunohistochemistry cytokine IL-6 and TNF- α ( stained area / total area , % ) . Statistical analysis: two-factor ANOVA , Bonferroni posttest . Results are expressed as mean ± SEM , n = 6 rats / group. Results: The table shows the CNP increases NOS activity in Wistar and SHR , however this increase was lower in hypertensive animals ( AW [ CNP- SF] = 104 ± 6; ΔSHR [ CNP- SF] = 84 ± 5 * , * p < 0.01 vs AW ) . W-S W-CNP SHR-S SHR-CNP SBP 121±3 120±5 178±3* 159±5^ NOS 85±6 189±2* 125±8* 209±5^ Media 66,8±9,0 68,3±2,1 104,9±10,2* 76,2±4,0^ Media/lumen 0,035±0,009 0,037±0,006 0,068±0,011* 0,043±0,007^ Elastin density 0,12±0,02 0,15±0,01 0,07±0,01* 0,12±0,01^ Picrosirius red 0,10±0,04 0,08±0,02 0,34±0,01* 0,19±0,03^ TGF-β 1,82±0,64 1,56±0,47 6,07±1,52* 2,51±0,44^ IL-6 0,7±0,4 0,5±0,3 19,2±0,8* 3,4±0,6^ TNF-α 1,4±0,3 0,9±0,4 18,5±0,9* 4,4±0,7^ *p