Reduction of Norepinephrine-Induced Tonic Contraction and Phosphoinositide Turnover in Arteries of Spontaneously Hypertensive Rats

Experiments were conducted to determine whether a difference in receptor-induced phosphatidylinosi- tol hydrolysis occurred in aorta from spontaneously hypertensive rats (SHR) v Wistar-Kyoto (WKY) rats, and whether such a difference was correlated with contractile response. Basal incorporation of 32P into phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol diphosphate (PIP2) and phosphatidic-acid (PA) was not different between SHR and WKY groups. However, after five minutes of norepinephrine (NE; 10 μmol) exposure, increases in 32P labeling were markedly lower in SHR arteries. The percentage decrease amounted to 45% for PI, 68% for PIP, 100% for PIP2 and 58% for PA. Basal incorporation of 3H-myo-inositol into inositol monophosphate (IP) was similar for SHR and WKY groups. However, after 30 minutes of NE (10 μmol), SHR arteries failed to show an increase in 3H-IP levels, whereas labeling was increased 219% in WKY arteries. The contractile response of SHR arteries to 10 μmol NE showed a marked reduction in the rate of development of the tonic phase that has previously been shown to be supported by activity of protein kinase C. Higher Ca2+ levels failed to augment the SHR response, whereas WKY responses were significantly increased. Contractions in the presence of the phorbol ester tetradecanoylphorbolacetate exhibited a similar reduction in NE-induced tonic phase tension. These results indicate an impairment in SHR arteries at the level of receptor-induced formation of inositol cycle second messengers, possibly due to elevated basal levels of protein kinase C. These differences may be important in explaining altered vascular responses in primary hypertension. Am J Hypertens 1989;2:40-45.