Abstract
Loss of supraspinal inputs to sympathetic preganglionic neurons causes a marked reduction in post‐ganglionic sympathetic vasoconstrictor nerve activity and sympathetic support of blood pressure in both humans and rats with spinal cord injury (SCI). The long‐term impact of this reduced sympathetic outflow on sympathetic neurotransmission is unknown. We investigated this question using established long‐term animal models of paraplegic (P, T2–3) and tetraplegic (T, C6–7) SCI in male Sprague Dawley rats (26 weeks in total age). Sixteen weeks after SCI, P and T rats showed significantly lower blood pressure than sham operated rats (P 103±2mmHg, T 97±4mmHg, sham 117±6mmHg) (P<0.05 P or T vs sham). P rats had faster heart rate (410±6bpm), while T rats had slower heart rate (299±10bpm) than sham rats (321±14bpm) (P<0.05, P or T vs sham). P and T rats also showed lower body weight than sham rats (P 380±5g, T 340±12g, sham 459±18g) (P<0.05, P or T vs sham). Small mesenteric arteries (MA) were collected from these rats for detailed examination of sympathetic neurotransmission. Norepinephrine (NE) release from sympathetic nerve terminals was measured using amperometry. ATP release was determined indirectly by measuring excitatory junction potentials (EJPs) in MA smooth muscle cells. Frequency dependent NE release curves in response to nerve stimulation were slightly leftward‐shifted in MA from P and T rats compared to sham rats. Interestingly, frequency dependent EJP response curves to nerve stimulation in MA of P and T rats were shifted markedly leftward and upward compared to sham rats; and responses in these rats also showed significant initially facilitation of EJPs during long‐train nerve stimulation. In pressurized MA, exogenous NE and ATP‐induced contractions were comparable in all rats. Immune staining of tyrosine hydroxylase in MA showed comparable sympathetic nerve density and distribution in all rats. NE content in tissues from left ventricle, kidney, spleen and MA were measured by HPLC. Compared to sham rats, NE content in left ventricle from P and T rats, and in MA from T rats, was significantly increased. NE content in MA from P rats was not different from sham rats, and NE content in kidney and spleen from P and T rats did not differ from sham animals. Our studies show that peripheral vascular NE, and especially ATP, release is enhanced during nerve stimulation 16 weeks after SCI, whereas post‐ganglionic nerve density and arterial reactivity to sympathetic neurotransmitters are unchanged. Even though overall sympathetic support of blood pressure is reduced after SCI, improvement in sympathetic neurotransmitter release may help maintain cardiovascular stability in long‐term SCI subjects. (Supported by NHLBI 2P01HL070687 and HL122223).Support or Funding InformationNHLBI 2P01HL070687 and HL122223This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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