title: Long-term captopril treatment restores natriuresis after carotid baroreceptor activation in the SHR.
abstract: In anesthetized Sprague-Dawley rats, intermittent bilateral carotid artery traction (BilCAT) caused a transient decrease in mean arterial pressure (MAP) of 28 +/- 3 mmHg and led to a progressive increase in sodium excretion (UNaV) that nearly doubled 45-90 min after initiation of the repetitive application of BilCAT (P < 0.001). This natriuresis was accompanied by an increase in glomerular filtration rate (GFR) from 2.70 +/- 0.3 to 3.2 +/- 0.3 ml/min (P < 0.001), no change in renal plasma flow [clearance of p-aminohippurate (PAH)], and an increase in the fractional excretion of lithium. Rats with bilateral renal denervation exhibited neither natriuresis nor an increase in GFR in response to BilCAT despite similar vasodepression caused by the maneuver. Normotensive Wistar-Kyoto (WKY) rats responded to BilCAT like Sprague-Dawley rats, whereas spontaneously hypertensive rats (SHR) exhibited an exaggerated vasodepressor response to BilCAT (-51 +/- 3 mmHg) without increasing either UNaV or GFR. Separate groups of WKY and SHR were treated from 4 wk of age with captopril added to the drinking water at a concentration of 1 g/l. At 12-14 wk, both groups had lower MAP compared with untreated animals. Captopril treatment did not alter either the natriuretic response or the increase in GFR seen in untreated WKY after BilCAT, and the maneuver produced equivalent degrees of vasodepression as in controls. However, treated SHR now responded to BilCAT with increases in both UNaV and GFR that closely resembled the responses seen in Sprague-Dawley and WKY rats. These results suggest that BilCAT produces natriuresis through a pathway dependent on the renal nerves. This pathway does not function in untreated SHR despite similar vasodepression. Long-term treatment with captopril restores this reflex pathway in SHR, lending support to the concept that angiotensin II is critically linked to heightened sympathetic nerve activity and abnormal sodium metabolism in this strain.
authors.affiliation: Division of Nephrology, San Francisco General Hospital, California, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Valentin
authors.forename: S A
authors.initials: SA
authors.lastname: Mazbar
authors.forename: M H
authors.initials: MH
authors.lastname: Humphreys
mesh_terms: D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D005919:Glomerular Filtration Rate; D006706:Homeostasis; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000294:innervation; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D010130:p-Aminohippuric Acid
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D010130:p-Aminohippuric Acid