Ramchandra, Rohit, Xing, Daniel T., Matear, Marcus, Lambert, Gavin, Allen, Andrew M., and May, Clive N. (2019) Neurohumoral interactions contributing to renal vasoconstriction and decreased renal blood flow in heart failure. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 317 (3). R386-R396.

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Abstract

In heart failure (HF), increases in renal sympathetic nerve activity (RSNA), renal norepinephrine spillover, and renin release cause renal vasoconstriction, which may contribute to the cardiorenal syndrome. To increase our understanding of the mechanisms causing renal vasoconstriction in HF, we investigated the interactions between the increased activity of the renal nerves and the renal release of norepinephrine and renin in an ovine pacing-induced model of HF compared with healthy sheep. In addition, we determined the level of renal angiotensin type-1 receptors and the renal vascular responsiveness to stimulation of the renal nerves and α1-adrenoceptors. In conscious sheep with mild HF (ejection fraction 35%–40%), renal blood flow (276 ± 13 to 185 ± 18 mL/min) and renal vascular conductance (3.8 ± 0.2 to 3.1 ± 0.2 mL·min−1·mmHg−1) were decreased compared with healthy sheep. There were increases in the burst frequency of RSNA (27%), renal norepinephrine spillover (377%), and plasma renin activity (141%), whereas the density of renal medullary angiotensin type-1 receptors decreased. In anesthetized sheep with HF, the renal vasoconstrictor responses to electrical stimulation of the renal nerves or to phenylephrine were attenuated. Irbesartan improved the responses to nerve stimulation, but not to phenylephrine, in HF and reduced the responses in normal sheep. In summary, in HF, the increases in renal norepinephrine spillover and plasma renin activity are augmented compared with the increase in RSNA. The vasoconstrictor effect of the increased renal norepinephrine and angiotensin II is offset by reduced levels of renal angiotensin type-1 receptors and reduced renal vasoconstrictor responsiveness to α1-adrenoceptor stimulation.

Item ID:	82159
Item Type:	Article (Research - C1)
ISSN:	1522-1490
Keywords:	cardiorenal syndrome type 2; heart failure; renal spillover; renal sympathetic nerve activity
Copyright Information:	© 2019 the American Physiological Society
Funders:	National Health and Medical Research Council (NHMRC)
Projects and Grants:	NHMRC 1020783, NHMRC 566819
Date Deposited:	26 Mar 2024 02:50
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100%
SEO Codes:	20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified @ 100%
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