Abstract
The purpose of this study was to determine whether the greater inhibitory effect of angiotensin II (Ang II) on urinary cAMP excretion in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats is secondary to hypertension and/or renal hemodynamic changes induced by Ang II. SHRs and WKY rats were treated chronically from conception, 6 weeks of age, or 10 weeks of age (n = 8–10) with the angiotensin-converting enzyme inhibitor captopril (100 mg/kg/day). A fourth group was not treated chronically with captopril (n = 7). At ∼13 weeks of age, all rats were anesthetized, given a bolus of captopril (30 mg/kg), and received an intrarenal infusion of a low dose of Ang II (1 ng/min). SHRs compared with WKY rats were normotensive, mildly hypertensive, and moderately hypertensive when treated with captopril from conception, 6 weeks of age, and 10 weeks of age, respectively, whereas untreated SHRs were severely hypertensive. In SHRs, Ang II decreased urinary cAMP excretion (p < .001), and this effect was independent of duration of captopril pretreatment (p = .696). In WKY rats, Ang II did not affect urinary cAMP excretion. Low-dose Ang II caused small and similar changes in renal blood flow and glomerular filtration rate in SHRs versus WKY rats and did not affect urine volume in either strain. We conclude that the greater effect of Ang II on urinary cAMP excretion in SHRs is not due to hypertension or to the renal hemodynamic effects of Ang II, but most likely to a greater effect of Ang II on some compartment of renal adenylyl cyclase activity in SHRs.
Footnotes
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Send reprint requests to: Edwin K. Jackson, Ph.D., 623 Scaife Hall, Center for Clinical Pharmacology, 200 Lothrop St., University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582. E-mail: edj+{at}pitt.edu
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↵1 This work was supported by National Institutes of Health Grants HL35909 and HL55314.
- Abbreviations:
- Ang II
- angiotensin II
- SHR
- spontaneously hypertensive rat
- WKY
- Wistar-Kyoto
- ACE
- angiotensin-converting enzyme
- PE
- polyethylene
- MABP
- mean arterial blood pressure
- LSD
- least-significant difference
- Received November 9, 1998.
- Accepted June 7, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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