Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats

Zofia Zukowska-Grojec, Maria Golczynska, Gregory H. Shen, Armida Torres-Duarte, Markus Haass, Claes R Wahlestedt, Adam K. Myers

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Neuropeptide Y (NPY) is a sympathetic cotransmitter and a platelet-derived factor which causes vasoconstriction, potentiation of norepinephrine (NE) action, and vascular mitogenic effects. Reciprocally, NE markedly enhances the actions of NPY. We studied vasopressor effects of NPY and sources of peptide release during the development of hypertension in spontaneously hypertensive rats (SHR). Conscious SHR (4 and 16 weeks old) had higher resting plasma levels of NE and epinephrine than age-matched Wistar-Kyoto (WKY) rats, but similar NPY immunoreactivity (NPY-ir) levels in platelet-poor plasmas (PPP). In both strains, NPY-ir levels in PPP were higher in 4-week-old than in older rats. However, at all ages (4-24 weeks) SHR had markedly elevated NPY-ir content in platelet-rich-plasmas than WKY rats, although levels declined with age and hypertension. In the superior mesenteric artery. NPY-ir content (per mg) was significantly higher in 4-week-old but lower in 16-week-old SHR than in WKY rats, suggesting greater sympatho-neural NPY stores and release (leading to depletion) during the development of hypertension. Four-week-old SHR also tended to have higher NPY-ir content in the adrenal medullae and coeliac ganglia but a lower content in the kidney than WKY rats; these differences disappeared with age. Pressor responsiveness to α-agonists and NPY were similar in both strains at 4 weeks. While unchanged by age in WKY rats, adrenergic and NPY-mediated vasopressor responses became augmented in 16- to 24-week-old SHR (compared with WKY rats); this hyperresponsiveness was not completely abolished by ganglionic blockade and not observed with vasopressin. The development of adrenergic hyperresponsiveness in SHR in the face of higher circulating catecholamines suggests a defect in downregulation of α-adrenoceptors. Since we have previously found that NPY can reverse pressor desensitization to NE, we postulate that increased release of platelet and sympatho-neural NPY leads to impaired adrenergic desensitization, whereas adrenergic/NPY interactions tesult in sensitization to NPY in SHR, and thus may contribute to vascular hyperreactivity and hypertrophy.

Original languageEnglish
Pages (from-to)845-852
Number of pages8
JournalPediatric Nephrology
Volume7
Issue number6
DOIs
StatePublished - Dec 1 1993
Externally publishedYes

Fingerprint

Neuropeptide Y
Inbred SHR Rats
Blood Vessels
Hypertension
Inbred WKY Rats
Adrenergic Agents
Norepinephrine
Blood Platelets
Sympathetic Ganglia
Platelet-Rich Plasma
Adrenal Medulla
Superior Mesenteric Artery
Vasoconstriction
Vasopressins
Adrenergic Receptors
Hypertrophy
Epinephrine
Catecholamines

Keywords

  • Hypertension
  • Neuropeptide Y
  • Norepinephrine
  • Platelet-derived
  • Sympathetic
  • Vascular hyperreactivity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats. / Zukowska-Grojec, Zofia; Golczynska, Maria; Shen, Gregory H.; Torres-Duarte, Armida; Haass, Markus; Wahlestedt, Claes R; Myers, Adam K.

In: Pediatric Nephrology, Vol. 7, No. 6, 01.12.1993, p. 845-852.

Research output: Contribution to journalArticle

Zukowska-Grojec, Zofia ; Golczynska, Maria ; Shen, Gregory H. ; Torres-Duarte, Armida ; Haass, Markus ; Wahlestedt, Claes R ; Myers, Adam K. / Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats. In: Pediatric Nephrology. 1993 ; Vol. 7, No. 6. pp. 845-852.
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