Serotonin hypersensitivity in aorta of two kidney-two clip hypertensive rats: calcium contribution and prostanoids-nitric oxide interactions.
Previous studies from our own laboratory have shown that abdominal aorta rings from two kidney - two clip hypertensive rats (HT) develop hypersensitivity to serotonin (SER) which is related to a decreased nitric oxide (NO) availability and enhanced thromboxane A2 production. In the present study we investigated whether calcium and prostanoid-NO interactions are involved in these findings. To this purpose, the aortic responses to SER were analyzed in calcium-free medium and in calcium-depleted aorta placed in normal medium. Moreover, effects of ridogrel (RID, an antagonist of TxA 2/PGH2 receptors and inhibitor of thromboxane synthetase) were analysed by cumulative dose-response curves to SER in the presence and in the absence of the NO synthase inhibitor N(omega)-nitro-L-arginine (NOLA). Vascular responses to SER in vessels from HT rats were associated with increased intracellular calcium mobilization. In addition, hypersensitivity to SER in HT group respect to sham group (SH) disappeared in the presence of RID, NOLA and RID plus NOLA. RID decreases the maximum tension to SER and this effect was prevented by NOLA. This inhibition was of a greater magnitude in rings from sham rats (SH): 34 +/- 6% than in HT rats: 15 +/- 6% (p < 0.05). Besides, RID decreased the sensibility to SER in the presence of NOLA only in the HT group. In conclusion, the present study suggests that SER hypersensitivity observed in HT rats is related to a facilitated intracellular calcium mobilization and enhanced TxA2-endoperoxide response. Changes in membrane SER-gated calcium channels opening are observed only during the early hypertensive period. Besides, the lower depressor effect of RID on the maximal tension to SER in aorta rings from HT rats are related with a decreased NO availability in this model of renovascular hypertension.
Rosón
M I
MI
Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad de Buenos Aires, Argentina. idelariv@fmed.uba.ar
Speziale
E
E
Celentano
M M
MM
Vega
G W
GW
Damiano
P F
PF
Puyó
A M
AM
de la Riva
I J
IJ
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D019335:Nitroarginine / Q000494:pharmacology; D010421:Pentanoic Acids / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013997:Time Factors
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D010421:Pentanoic Acids; D011453:Prostaglandins; D011725:Pyridines; D019335:Nitroarginine; D012701:Serotonin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011451:Prostaglandin-Endoperoxide Synthases; C060219:ridogrel; D002118:Calcium