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Pharmacological dissection of vascular effects caused by activation of protease‐activated receptor 1 and 2 in anesthetized rats
Author(s) -
Cicala Carla,
Morello Silvana,
Santagada Vincenzo,
Caliendo Giuseppe,
Sorrentino Ludovico,
Cirino Giuseppe
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0633fje
Subject(s) - protease , receptor , chemistry , pharmacology , dissection (medical) , anesthesia , medicine , anatomy , biochemistry , enzyme
To clarify the role of protease‐activated receptor 1 and 2 (PAR‐1 and PAR‐2) in controlling blood pressure, we evaluated changes in blood pressure induced by a peptide that activates the receptor PAR‐1 (PAR‐1AP, SFLLRNPND) and a peptide that activates the receptor PAR‐2 (PAR‐2AP, SLIGRL) in naive and ganglion‐blocked anesthetized rats. The role of nitric oxide on the effects observed was also investigated. Intravenous injection of PAR‐1AP induced a biphasic change in mean arterial blood pressure (MABP) characterized by hypotension followed by hypertension, the latter was enhanced strongly by ganglion‐blockade. After L‐NAME infusion in ganglion‐blocked rats, hypertension induced by PAR‐1AP was still increased, which returned to control value after L‐arginine infusion. L‐NAME did not inhibit PAR‐1AP–induced hypotension. Intravenous injection of PAR‐2AP induced a biphasic change in MABP, characterized by hypotension followed by a hypertensive phase that reached the maximum value in 5–6 min. Hypertension was abolished by ganglion‐blockade and was restored by an infusion of L‐NAME. This effect was reverted by L‐arginine. L‐NAME reduced the duration of hypotension induced by PAR‐2AP. In conclusion, we define that PAR‐1 mainly mediates hypertension, whereas PAR‐2 mainly is responsible for hypotension. Furthermore, we give evidence for a hypertensive effect of PAR‐2AP linked to a reflex mechanism that is modulated by nitric oxide.