(269c) Interfacial Horseradish Peroxidase Spot Growth in the Aorta of Acute Hypertensive & Hypotensive Rats
Atherosclerosis is by far the leading cause of death in all Western countries. It begins with the transport into and accumulation in the artery wall of low-density lipoprotein cholesterol (LDL) under conditions where blood LDL concentration is high and eventually develops into lesions. In earlier theoretical work, our group explained historic data to establish that this transport is convection-dominated. We later developed a theory to account for Tedgui & Lever and Baldwin & Wilson's measured dependence on the vessel's transmural pressure (Δp) of the aorta's hydraulic conductivity (Lp), the ratio of the resulting transmural convection to an imposed Δp. With increasing Δp, Lp initially drops and then is flat over the balance of the physiological range. Our model attributes the intial drop to intimal compression by a factor of 5 and an associated blocking by endothelial cells of the internal elastic lamina's fenestrae under pressure loading, with no further compression. This theory invokes pressure-independent values endothelial and medial Lps. Using this and an intimal compaction-free theory, we predicted how Δp would affect how a macromolecular tracer (horseradish peroxidase ? HRP) that crosses the endothelium through an isolated endothelial leak, would spread subendothelially with time for constant tissue properties. With intimal compaction the theory predicts spots whose asymptotic sizes decrease (at a faster rise time) with Δp while, without it, their ultimate sizes remain the same. In this paper we test these results by measuring the growth of HRP spots with HRP circulation time for normal, acute hypertensive and acute hypotensive rats. We use rats whose pressure is only acutely changed in order to exclude vessel remodeling that would change the vessel's intrinsic endothelial and medial Lp. Our results for normotensive rats are consistent with earlier measurements (Chuang et al, 1990). We induce acute hypertension (180 mmHg) with norepinephrine and acute hypotension (45 mmHg) with nitroprusside and labetalol. We measure Lp of the aorta as a function of Δp, first without, then with one of these agents on the same vessel to verify that the chemical does not affect tissue properties. Norepinephrine's effect on Lp is well within the error bars of the drug-free measurements, but nitroprusside and labetalol changed Lp substantially. To induce acute hypotension, we instead opened the rat's chest and with a hook held the exposed heart. Our HRP spot growth measurements show a clear decrease in asymptotic spot size with increasing Δp and, for the two higher pressures, a rise time decrease. We compare these results with the above-mentioned theory and extend the theory to include the effects (that we measure) of nitroprusside and labetalol on the intrinsic Lp of the endothelium and media. We compare HRP spot growth in the presence of these agents with the results of this extended theory.