MODULATION OF VASCULAR FUNCTION BY NEUROPEPTIDE-Y DURING DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

Neuropeptide Y (NPY) is a sympathetic cotransmitter and a platelet-der ived factor which causes vasoconstriction, potentiation of norepinephr ine (NE) action, and vascular mitogenic effects. Reciprocally, NE mark edly enhances the actions of NPY. We studied vasopressor effects of NP Y and sources of peptide release during the development of hypertensio n in spontaneously hypertensive rats (SHR). Conscious SHR (4 and 16 we eks old) had higher resting plasma levels of NE and epinephrine than a ge-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 p latelet-rich-plasmas than WKY rats, although levels declined with age and hypertension. In the superior mesenteric artery, NPY-ir content (p er 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 a nd release (leading to depletion) during the development of hypertensi on. Pour-week-old SHR also tended to have higher NPY-ir content in the adrenal medullae and coeliac ganglia but a lower content in the kidne y than WKY rats; these differences disappeared with age. Presser respo nsiveness to alpha-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 (com pared with WKY rats); this hyperresponsiveness was not completely abol ished by ganglionic blockade and not observed with vasopressin. The de velopment of adrenergic hyperresponsiveness in SHR in the face of high er circulating catecholamines suggests a defect in downregulation of a -adrenoceptors. Since we have previously found that NPY can reverse pr esser desensitization to NE, we postulate that increased release of pl atelet and sympatho-neural NPY leads to impaired adrenergic desensitiz ation, whereas adrenergic/NPY interactions result in sensitization to NPY in SHR, and thus may contribute to vascular hyperreactivity and hy pertrophy.