VASCULAR STRUCTURAL AND FUNCTIONAL ALTERATIONS BEFORE AND AFTER THE DEVELOPMENT OF HYPERTENSION IN SHR

The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dysfunction, in human and experimental hypertension is still unclear. Moreover, the interrelationships between structural and functional vascular alterations are presently under debate. The aim of this study was to assess the arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as compared to age-matched normotensive Wistar-Kyoto rats (WKY). Seventeen SHR (4 to 12 weeks old) and 17 WKY were included in the study. Blood pressure was measured noninvasively. After killing the animals, relative left ventricular mass (RLVM) was calculated, and mesenteric arcades were dissected and mounted on a micromyograph. Functional and structural characteristics of the vessels were measured: media thickness (MT), media/lumen ratio (M/L), and wall tension in response to norepinephrine and acetylcholine. At 4 weeks of age, no difference in blood pressure and RLVM between SHR and WKY was detected, but MT and M/L of mesenteric small resistance arteries were significantly greater in SHR, An increased response to norepinephrine was observed in terms of wall tension, but not of active media stress at the two higher norepinephrine concentrations. No difference in the dose-response curve to acetylcholine between SHR and WKY was observed. At 8 and 12 weeks of age systolic blood pressure was significantly higher in SHR; RLVM, MT, and M/L were also higher at this stage. Small resistance arteries of SHR showed an increased response to norepinephrine (in terms of wall tension, but not of active media stress) and a reduced response to acetylcholine with respect to WKY when evaluated at 12 weeks of age. In conclusion, we observed an evident vascular hypertrophy at 4 weeks of age, before the onset of increased cardiac weight and before the development of hypertension. An enhanced contractile response to norepinephrine, related to vascular hypertrophy, was detectable in 4-week-old SHR, whereas endothelial dysfunction, as expressed by the dose-response curve to acetylcholine, was not evident. Endothelial dysfunction was observed only in 12-week-old SHR, after development of hypertension and cardiac hypertrophy, supporting the hypothesis that a hemodynamic rather than a structural factor may be involved in its genesis.