RESUMEN
AIMS: Our aim was to evaluate whether tirofiban, which mimics the structure of arginine-glycine-aspartic acid (RGD) peptides, up-regulates soluble guanylate cyclase beta1 subunit (sGC-beta1) expression in vascular smooth muscle cells (VSMCs) and in aorta from rats, and to investigate the pharmacological and pathophysiological consequences of this up-regulation. METHODS AND RESULTS: Wistar, Wistar Kyoto, and spontaneously hypertensive rats (SHRs) were used. sGC-beta1 content was assessed by immunoblotting. Arterial pressure was recorded using a tail-cuff sphygmomanometer. Sodium nitroprusside (SNP) and isosorbide dinitrate (IDN) were used as nitric oxide (NO) donors. Tirofiban increased the sGC-beta1 content in VSMCs and in aortic walls from rats after 6 h of treatment. Rats treated with tirofiban experienced a more pronounced decrease in their arterial pressure after acute SNP treatment than vehicle-treated rats. Isolated rat aortic rings incubated with tirofiban showed a higher relaxing response to SNP than control rings as well as an increased sGC-beta1 content and SNP-induced cyclic guanosine monophosphate synthesis. Animals receiving IDN for 1 week showed decreased sGC-beta1 in aortic walls and did not respond to SNP treatment with changes in arterial pressure. Tirofiban restored the decreased sGC-beta1 content in IDN-treated rats and promoted a decreased arterial pressure in response to SNP administration. SHRs showed reduced sGC-beta1 levels, and tirofiban increased these levels and led to a higher response to SNP. CONCLUSION: Tirofiban increased the sGC-beta1 content in contractile cells and aortic walls of rats, enhancing the response to SNP and reversing the NO donor tachyphylaxis.
