Restoration of reflex natriuresis following bilateral carotid baroreceptor activation by long-term captopril treatment in the spontaneously hypertensive rat J.P. Valentin, S.A. Mazbar, M.H. Humphreys. Dept of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA

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.

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Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00568.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. H2434-H2440 ◽

Cited By ~ 51

Author(s):

Eva H. C. Tang ◽

Michel Feletou ◽

Yu Huang ◽

Ricky Y. K. Man ◽

Paul M. Vanhoutte

Keyword(s):

Sodium Nitroprusside ◽

Spontaneously Hypertensive Rat ◽

Isometric Force ◽

Calcium Ionophore ◽

Soluble Guanylyl Cyclase ◽

Inhibitory Effect ◽

Previous Exposure ◽

Spontaneously Hypertensive ◽

A 23187

Preliminary studies suggested that previous exposure to acetylcholine (ACh) exerts a delayed inhibition of subsequent contractions mediated by endothelium-derived contracting factor (EDCF). To confirm this long-term inhibitory effect of ACh and to determine whether nitric oxide (NO) mediates the phenomenon, we suspended rings of spontaneously hypertensive rat (SHR) aortas in organ chambers for the recording of isometric force. The rings were incubated in the absence or presence of Nω-nitro-l-arginine methyl ester (l-NAME; inhibitor of NO synthases) or 1 H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ; inhibitor of soluble guanylyl cyclase) before exposure to increasing concentrations of ACh or sodium nitroprusside (SNP) during contractions to phenylephrine. Thereafter, EDCF-mediated contractions to ACh or the calcium ionophore A-23187 were elicited. If the rings were preexposed to ACh or SNP, the subsequent ACh-induced EDCF-mediated contractions were reduced compared with those obtained in rings of the same arteries not previously exposed to either agent. ODQ did not affect the inhibition caused by preexposure to ACh but significantly reduced that caused by preexposure to SNP. Previous exposure to SNP reduced, whereas previous exposure to ACh did not affect, endothelium-dependent contractions to A-23187. Previous exposure to either ACh or SNP did not affect the contractions to the thromboxane mimetic U-46619. Thus ACh and SNP exert delayed inhibition of EDCF-mediated contractions via distinct pathways. The effect of ACh is NO independent and upstream of the increase in calcium concentration that triggers the release of EDCF. The effect of SNP is downstream of the calcium rise and is mainly NO dependent.

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