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Muscarinic and β-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase
| Content Provider | Semantic Scholar |
|---|---|
| Author | Vandecasteele, Grégoire Eschenhagen, Thomas Scholz, Hasso Stein, Birgitt Verde, Ignacio Fischmeister, Rodolphe |
| Copyright Year | 1999 |
| Abstract | >Nitric oxide (NO) is an ubiquitous signaling molecule produced from L-arginine by NO synthase (NOS). In the vasculature, NO mediates parasympathetic endothelium-dependent vasodilation. NO may also mediate the parasympathetic control of myocardial function. This is supported by the observations that NOS3, the endothelial constitutive NOS, is expressed in normal cardiac myocytes from rodents and human, and NOS and/or guanylyl cyclase inhibitors antagonize the effect of muscarinic agonists on heart rate, atrio–ventricular conduction, contractility and L-type calcium current. Here we examine the autonomic regulation of the heart in genetically engineered mice deficient in NOS3 (NOS3-KO)(ref. 8). We show that the chronotropic and inotropic responses to both β-adrenergic and muscarinic agonists were unaltered in isolated cardiac tissue preparations from NOS3-KO mice, although these mice have a defective parasympathetic regulation of vascular tone. Similarly, β-adrenergic stimulation and muscarinic inhibition of the calcium current did not differ in cardiac myocytes from NOS3-KO mice and those from wild-type mice. RT–PCR did not demonstrate upregulation of other NOS isoforms. Similarly, Gi/Go proteins and muscarinic receptor density were unaltered. These data refute the idea that NOS3 is obligatory for the normal autonomic control of cardiac muscle function. |
| Starting Page | 331 |
| Ending Page | 334 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| DOI | 10.1038/6553 |
| Alternate Webpage(s) | http://ubibliorum.ubi.pt/bitstream/10400.6/561/1/t01812pdf.pdf |
| Alternate Webpage(s) | https://doi.org/10.1038/6553 |
| Volume Number | 5 |
| Journal | Nature Medicine |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |