Increased inositol 1,4,5-trisphosphate binding capacity in vascular smooth muscle of spontaneously hypertensive rats.
High intracellular levels of free calcium (Ca2+) are found in cells of hypertensive patients, and these levels have been correlated with increased blood pressure. In the present study, we characterized inositol 1,4,5-trisphosphate (InsP3) receptors in aorta and heart microsomes of Long-Evans rats. We also studied this receptor in some organs of spontaneously hypertensive rats (SHR) to clarify the role this important component of the mechanism of Ca2+ regulation has in hypertension. Microsomal fractions were prepared from aorta, heart, adrenal cortex (organs directly involved in the regulation of blood pressure), and cerebellum (control organ, not directly involved) of 14-week-old SHR and Wistar-Kyoto (WKY) rats. InsP3, receptors were studied in each microsomal fraction by a radioligand binding method with [3H]InsP3. The properties of InsP3 binding sites in each tissue were consistent with those of well-characterized InsP3 receptors: 1) InsP3 binding was specific and saturable, 2) InsP3 binding increased upon pH elevation, 3) InsP3 binding was inhibited by heparin, and 4) InsP3 had a higher binding affinity than InsP4. No significant difference of binding affinity or of maximal binding capacity between WKY and SHR was observed in microsomes from heart, adrenal cortex, and cerebellum. It is interesting that InsP3 binding capacity of SHR aorta microsomes was significantly higher (1.6 fold) than that of WKY aorta microsomes. These results suggest that increased InsP3 receptor activity in vascular smooth muscle of SHR may contribute to the elevation of blood pressure. Further studies are needed to assess the significance of this observation as regards the mobilization of intracellular Ca2+.
Bernier
S
S
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Guillemette
G
G
D000818:Animals; D001011:Aorta / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D015544:Inositol 1,4,5-Trisphosphate