23 September 2008
We investigated pivotal signalling responses of cultured aortic smooth muscle cells (VSMC) from the spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto rat (WKY) to lipoproteins. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL<sub>3</sub>) stimulated a time- and dose-dependent accumulation of inositol phosphates in VSMC. SHR and WKY VSMC exhibited comparable half-maximal dose requirements (≈13 µg/ml for LDL and ≈14 µg/ml for HDL<sub>3</sub>), although, at any given dose, the response of SHR VSMC was significantly greater than WKY VSMC. Simultaneous addition of LDL and HDL<sub>3</sub> to VSMC resulted in additive stimulatory effects on phosphoinositide catabolism. Pertussis toxin pretreatment of VSMC completely negated the stimulatory effects of LDL and HDL<sub>3</sub> on IP accumulation. [<sup>32</sup>P]-ADP ribosylation and immunoblotting studies revealed the guanine nucleotide-binding (G protein) substrate(s) for pertussis toxin to be a G<sub>i</sub> protein(s). SHR and WKY VSMC did not differ with respect to levels of G<sub>iα</sub> or G<sub>β</sub>, and, thus, the amplified responsiveness in SHR VSMC cannot be attributed to alterations in levels of pertussis toxin-sensitive G protein. The spectrum of signalling responses elicited by LDL and HDL<sub>3</sub> are similar to those elicited by vasoactive hormones, and thus lipoproteins may, via stimulation of phosphoinositide catabolism, <sup>45</sup>Ca<sup>2+</sup> uptake and Na<sup>+</sup>/H<sup>+</sup>-exchange, directly regulate smooth muscle cell growth and contraction.