1. There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this phenomenon is generic to sympathetic transmission to smooth muscle rather than a purely vascular phenomenon. We sought the origin of the effect by successively blocking the buffering effects of the neuronal monoamine transporter, prejunctional α 2-adrenoceptors and NO from nitrergic nerves with desipramine (0.1 μM), rauwolscine (0.01 μM) and L-N G-nitro-arginine (100 μM). 2. In the presence of desipramine, contractile responses to electrical field stimulation but not to noradrenaline (1 nM-100 μM) were greater in SHR than in Wistar-Kyoto (WKY). Neither inhibition of prejunctional α 2-adrenoceptors nor the blockade of neuronal nitric oxide synthase (nNOS) accounted for the differential enhancement of response in SHR. The enhanced effectiveness of motor neurotransmission in SHR becomes most apparent when all known major buffering mechanisms are removed. 3. When nitrergic responses were isolated pharmacologically (phentolamine 1 μM and guanethidine 30 μM; tone raised with carbachol 50 μM), they were not different between SHR and WKY. 4. Western blots showed that both nNOS and tyrosine hydroxylase are expressed to a similar extent in anococcygeus muscle from SHR and WKY, suggesting similar adrenergic and nitrergic innervations in the two strains. This suggests that enhanced motor transmission is due to increased transmitter release per varicosity rather than there being normal transmission from a greater number of sites. 5. We conclude that there is a generic enhancement of sympathetic transmission in SHR rather than this being a vascular phenomenon.
|Journal||British Journal of Pharmacology|
|Publication status||Published - 1 Oct 2003|
- Adrenergic innervation
- Anococcygeus muscle
- Noncholinergic innervation