Abstract
To characterize the effects of renal sympathetic nerve activation (RSNA) on renal purine secretion, 13 perfused rat kidneys were stimulated with periarterial electrodes at 7 Hz for 3 min, and purine secretion was determined by measuring with high-performance liquid chromatography purines in the renal venous perfusate 1 min before and during the last minute of RSNA. RSNA significantly increased renal perfusion pressure and significantly increased the secretion of adenosine and adenosine metabolites (inosine, hypoxanthine, and xanthine) by 2- to 5-fold. To investigate the participation of α- and β-adrenoceptors in this response, four groups of perfused kidneys (n = 5/group) were pretreated with either vehicle, prazosin (α1-adrenoceptor antagonist; 0.03 μM), phentolamine (α1/2-adrenoceptor antagonist; 3 μM), or propranolol (β1/2-adrenoceptor antagonist; 0.1 μM), and purine secretion was measured before and during RSNA at 1, 3, 5, 7, and 9 Hz. Prazosin, phentolamine, and propranolol abolished the RSNA-induced increase in the secretion of adenosine, inosine, hypoxanthine, and xanthine. In contrast, prazosin and phentolamine nearly abolished, whereas propranolol only slightly reduced, renal vascular responses to RSNA. Our results indicate that RSNA increases renal purine secretion via a mechanism that requires both α- and β-adrenoceptors. It is well known that in the kidney adenosine activates renal afferent nerves, enhances renovascular responses to norepinephrine and angiotensin II, and increases sodium reabsorption; therefore, RSNA-induced adenosine production may contribute to the hypertensive effects of RSNA. Moreover, the antihypertensive effects of β-adrenoceptor antagonists may in part be due to inhibition of RSNA-induced renal adenosine production.
Footnotes
-
Send reprint requests to: Edwin K. Jackson, Doctor of Philosophy, Center for Clinical Pharmacology, University of Pittsburgh Medical Center, 623 Scaife Hall, 200 Lothrop St., Pittsburgh, PA. E-mail: edj+{at}pitt.edu
-
↵1 This work was supported by National Institutes of Health Grants HL55314 and HL35909.
- Abbreviation:
- RSNA
- renal sympathetic nerve activation
- Received March 24, 1998.
- Accepted August 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|