These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Functional study of the [Ca2+]i signaling pathway in aortas of L-NAME-hypertensive rats.
    Author: de Campos Grifoni S, Bendhack LM.
    Journal: Pharmacology; 2004 Mar; 70(3):160-8. PubMed ID: 14752236.
    Abstract:
    A variety of mechanisms has been proposed to suggest that nitric oxide participates in the regulation of smooth muscle free [Ca(2+)](c) (the primary determinant of contractile tone), including inhibition of Ca(2+) influx across the plasma membrane and inhibition of intracellular Ca(2+) release. In view of such considerations, the aim of this study was to investigate the possible alterations in contractile responses induced by drugs that mobilize Ca(2+) from different sources in aortae from N(G)-nitro-L-arginine methyl ester (L-NAME) hypertensive rats (LHR). Treatment with L-NAME did not alter the contractile response induced by phenylephrine; however, indomethacin increased the contraction to phenylephrine only in LHR aortae (1.36 +/- 0.08 g, n = 6, vs. 1.97 +/- 0.09 g, n = 7). Both phenylephrine and caffeine evoked rapid and phasic contractions in intact or denuded aortic rings in Ca(2+)-free solution containing EGTA. Phenylephrine-elicited phasic contractions were lower in normotensive rats (NR; 0.41 +/- 0.05 g, n = 9) than in LHR (0.57 +/- 0.06 g, n = 6) and were increased by endothelium removal only in the NR group (0.64 +/- 0.05 g, n = 6). Conversely, neither with treatment with L-NAME nor endothelium removal altered the phasic contractile responses induced by caffeine. The Ca(2+) influx stimulated with phenylephrine was greater in NR (1.95 +/- 0.08 g; pD(2) 6.06 +/- 0.69; n = 8) than in the LHR denuded aorta (1.63 +/- 0.11 g; pD(2) 3.52 +/- 0.06; n = 6). Similarly, contractions stimulated with phorbol ester in denuded arteries were greater in NR (1.76 +/- 0.08 g, n = 7) than in LHR (1.11 +/- 0.11 g, n = 7). In the same manner, indomethacin failed to alter the contraction stimulated with phorbol ester in NR arteries (2.01 +/- 0.21 g, n = 7), although it completely blocked the inhibitory effect of chronic treatment with L-NAME on this contractile response (1.94 +/- 0.24 g; n = 9). Indomethacin did not change the contractile responses stimulated by increasing concentrations of extracellular Ca(2+) in either NR aortas (1.44 +/- 0.26 g; pD(2) 4.74 +/- 0.79; n = 6) or LHR aorta (1.99 +/- 0.19 g; pD(2) 4.10 +/- 0.47; n = 8). However, in the presence of indomethacin, the Ca(2+) influx was similar in NR and LHR aortae. Taken together, these results suggest that, in this model of hypertension, the increase in agonist-induced release of Ca(2+) from intracellular stores may be partly compensated by inhibition of Ca(2+) influx and that this effect is due to the increased production of the relaxant prostanoid in vascular smooth muscle cells.
    [Abstract] [Full Text] [Related] [New Search]