Norepinephrine secretion

Abstract: Studies from our laboratory suggest that the afferent renal nerves from the clipped kidney enhance sympathetic nervous system activity in established one-kidney, one clip and two-kidney, one clip Goldblatt hypertension. Because adenosine is released during renal ischaemia and adenosine has been shown to increase the frequency of afferent renal nerve signals, we proposed the hypothesis that intrarenal adenosine might produce hypertension by activating the sympathetic nervous system via the afferent renal nerves. To examine this hypothesis, changes in arterial pressure and activity of the sympathetic nervous system were measured during renal artery infusion of adenosine before and after renal denervation in uninephrectomized sodium replete conscious dogs. Intrarenal adenosine infusion produced a 21 +/- 3 mmHg mean arterial pressure rise in association with an increase in plasma norepinephrine. Ganglionic blockade during intrarenal adenosine infusion resulted in a significantly greater decrease in arterial pressure compared to control responses. After renal denervation, intrarenal adenosine infusion resulted in no change in arterial pressure, plasma norepinephrine or arterial pressure response to ganglionic blockade. To further assess sympathetic activity changes, right renal norepinephrine secretion and multifibre efferent neural traffic were measured during left renal artery adenosine infusion in alpha-chloralose-anaesthetized dogs. Left renal artery adenosine infusion resulted in increased right renal vascular resistance in association with increased renal norepinephrine secretion and increased efferent neural activity. The data indicate that in the dog with intact renal nerves, intrarenal adenosine produces hypertension by activating the sympathetic nervous system.

Abstract: Brain stimulation or activation of certain reflexes can result in differential activation of the two populations of adrenal medullary chromaffin cells: those secreting either epinephrine or norepinephrine, suggesting that they are controlled by different central sympathetic networks. In urethan-chloralose-anesthetized rats, we found that antidromically identified adrenal sympathetic preganglionic neurons (SPNs) were excited by stimulation of the rostral ventrolateral medulla (RVLM) with either a short (mean: 29 ms) or a long (mean: 129 ms) latency. The latter group of adrenal SPNs were remarkably insensitive to baroreceptor reflex activation but strongly activated by the glucopenic agent 2-deoxyglucose (2-DG), indicating their role in regulation of adrenal epinephrine release. In contrast, adrenal SPNs activated by RVLM stimulation at a short latency were completely inhibited by increases in arterial pressure or stimulation of the aortic depressor nerve, were unaffected by 2-DG administration, and are presumed to govern the discharge of adrenal norepinephrine-secreting chromaffin cells. These findings of a functionally distinct preganglionic innervation of epinephrine- and norepinephrine-releasing adrenal chromaffin cells provide a foundation for identifying the different sympathetic networks underlying the differential regulation of epinephrine and norepinephrine secretion from the adrenal medulla in response to physiological challenges and experimental stimuli.

Abstract: α‐Latrotoxin (LTX) stimulates massive neurotransmitter release by two mechanisms: Ca 2+ ‐dependent and ‐independent. Our studies on norepinephrine secretion from nerve terminals now reveal the different molecular basis of these two actions. The Ca 2+ ‐dependent LTX‐evoked vesicle exocytosis (abolished by botulinum neurotoxins) is 10‐fold more sensitive to external Ca 2+ than secretion triggered by depolarization or A23187; it does not, however, depend on the cation entry into terminals but requires intracellular Ca 2+ and is blocked by drugs depleting Ca 2+ stores and by inhibitors of phospholipase C (PLC). These data, together with binding studies, prove that latrophilin, which is linked to G proteins and inositol polyphosphate production, is the major functional LTX receptor. The Ca 2+ ‐independent LTX‐stimulated release is not inhibited by botulinum neurotoxins or drugs interfering with Ca 2+ metabolism and occurs via pores in the presynaptic membrane, large enough to allow efflux of neurotransmitters and other small molecules from the cytoplasm. Our results unite previously contradictory data about the toxin9s effects and suggest that LTX‐stimulated exocytosis depends upon the co‐operative action of external and intracellular Ca 2+ involving G proteins and PLC, whereas the Ca 2+ ‐independent release is largely non‐vesicular.