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ALTERED SIGNALLING IN VASCULAR SMOOTH MUSCLE FROM SPONTANEOUSLY HYPERTENSIVE RATS MAY LINK MEDIAL HYPERTROPHY, VESSEL HYPERINNERVATION AND ELEVATED NERVE GROWTH FACTOR
Author(s) -
Tuttle Jeremy B.,
Spitsbergen John M.,
Stewart Jeanine S.,
McCarty Richard M.,
Steers William D.
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02845.x
Subject(s) - medicine , endocrinology , vascular smooth muscle , forskolin , nerve growth factor , phenylephrine , secretion , growth factor , biology , platelet derived growth factor receptor , spontaneously hypertensive rat , stimulation , receptor , chemistry , smooth muscle , blood pressure
Summary 1. Secretion of nerve growth factor (NGF) by cultured vascular smooth muscle cells (VSMC) derived from spontaneously hypertensive rats (SHR) and the normotensive Wistar‐Kyoto (WKY) strain was measured via two site immuno‐assay (ELISA). 2. Basal NGF secretion rates of quiescent SHR VSMC in serum‐free culture medium were elevated compared to similar WKY VSMC. 3. SHR VSMC displayed increased NGF secretion in response to activation of sympathetic neurotransmitter receptors while VSMC of WKY were largely unresponsive to the agents (phenylephrine, isoproterenol, alpha‐beta‐methyl ATP, neuro‐peptide Y). 4. Mitogenic stimulation with platelet‐derived growth factor (PDGF) raised SHR NGF secretion rates almost three times more than PDGF increased WKY secretion. 5. SHR VSMC also failed to demonstrate normal inhibitory control over NGF secretion seen in WKY and previously in Sprague‐Dawley and Wistar strain VSMC with adenylate cyclase activation and down‐regulation of protein kinase C. High concentrations of forskolin stimulated, instead of inhibiting, secretion in SHR. Stimulation was also seen after pre‐treatment with phorbol ester for 24 h while this inhibited secretion in the WKY. 6. These results confirm that the SHR VSMC are hyper‐responsive to growth stimuli such as contractile agonists and mitogens. This hyperresponsiveness includes an abnormal control over NGF secretion such that normally inhibitory treatments stimulate NGF output in the SHR. 7. Because the SHR demonstrates important defects in the major intracellular growth‐signalling systems that also regulate NGF output and vessel innervation, the predicted result of the defects is a destructive feed‐forward cycle of growth and innervation. This is the SHR phenotype in vivo .