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Defective ANF-R2/ANP-C receptor-mediated signalling in hypertension

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Abstract

In the present studies we have shown that atrial natriuretic factor (peptide) receptor of ANF-R2/ANP-C type is coupled to adenylyl cyclase/cAMP signal transduction system through Gi-regulatory protein and is implicated in mediating some of the physiological responses of atrial natriuretic factor or peptide (ANP). ANF-R2/ANP-C receptor-mediated adenylyl cyclase inhibition was altered in hypertension. This alteration was tissue specific. In heart, aorta, brain and adrenal, the extent of inhibition of adenylyl cyclase by ANP was enhanced in SHR as compared to age-matched WKY, whereas in platelets, the ANP-mediated inhibition was completely attenuated. The enhanced inhibition of adenylyl cyclase by ANP was also observed in heart and aorta from DOCA-salt hypertensive rats. In addition, the augmented inhibition of adenylyl cyclase by ANP was observed in 2 weeks and older ANP but not in 3–5 days old SHR. Similarly, in DOCA-salt hypertensive rats, the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of DOCA-salt treatment when the blood pressure was also enhanced, however one week of DOCA-salt treatment did not result in an augmented blood pressure and augmented ANP-mediated inhibition of adenylyl cyclase, suggesting that blood pressure increase may be responsible for the enhanced responsiveness of ANP to adenylyl cyclase inhibition. However, in genetic model of hypertension, the increased inhibition of adenylyl cyclase by ANP at 2 weeks of age (when the blood pressure is normal) may be implicated in the pathogenesis of hypertension. The augmented inhibition of adenylyl cyclase in cardiovascular tissues from SHR and DOCA-salt hypertensive rats may be due to the upregulation of ANF-R2/ANP-C receptors or due to the amplification of post-receptor signalling mechanisms.

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Abbreviations

BNP:

brain natriuretic peptide

ANP:

atrial natriuretic peptide or factor

CNP:

C-type natriuretic peptide

GC:

guanylyl cyclase

NPR:

natriuretic peptide receptor

Gs:

stimulatory guanine nucleotide regulatory protein

Gi:

inhibitory guanine nucleotide regulatory protein

WKY:

Wistar-Kyoto rats

SHR:

spontaneously hypertensive rats

PT:

pertussis toxin

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  1. Groupe de recherche sur le système nerveux autonome, Department of Physiology, Faculty of Medicine, University of Montreal, Succ. centre-ville, C.P. 6128, H3C 3J7, Montreal, (Québec), Canada

    Josée Marcil & Madhu B. Anand-Srivastava (recipient of the Medical Research Council Scientist Award from the Medical Research Council of Canada)

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  1. Josée Marcil
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Marcil, J., Anand-Srivastava, M.B. Defective ANF-R2/ANP-C receptor-mediated signalling in hypertension. Mol Cell Biochem 149, 223–231 (1995). https://doi.org/10.1007/BF01076581

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