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A variety of pathological conditions, such as hypertension, congestive heart failure, and diabetes is associated with changes in frequency and amplitude of sympathetic-mediated blood pressure oscillations (Mayer waves). It is still unclear how the vasculature contributes to changes in these oscillations. We examined the hypothesis that α1-adrenoceptor density and subtype expression determine magnitude and speed of catecholamine-induced contraction in vascular smooth muscle cells (VSMCs) and mesenteric arterioles. Primary VSMCs from rat aorta were transfected with genes encoding the α1D/A-, α1B- or α1A/C-adrenoceptor subtypes (n=12 in each group). The α1-adrenoceptor agonist phenylephrine produced dose dependent contraction of VSMCs that was greater in all three transfected groups compared to controls (3.0±0.3, 4.5±0.5, 5.1±0.7, 4.8±0.6%, controls vs. α1D/A, α1B, α1A/C at 10-6 M, p<0.05). Speed of contraction was almost doubled in transfected cells (0.42±0.04, 0.74±0.08, 0.78±0.13, 0.89±0.1 %/s, controls vs. α1D/A, α1B, α1A/C at 10-7 M, p<0.05). No differences were found between the three transfected groups. Contraction in response to KCl depolarization did not differ between groups. These results were confirmed in isolated pressurized mesenteric arterioles from spontaneously hypertensive rats and renal hypertensive Wistar Kyoto rats, that are known to differ in vascular α1-adrenergic receptor density. Interestingly, data obtained in isolated arterioles correspond with the differences found in Mayer waves of these two rat groups. In conclusion, vascular α1-adrenoceptor density determines magnitude and speed of sympathetic-mediated contraction in VSMCs and isolated arterioles. Furthermore, α1-adrenoceptor subtype expression does not appear to influence sympathetic-mediated vasoconstriction. Altered vascular responsiveness to catecholamines due to changes in α1-adrenoceptor density may explain the frequency shift and amplitude changes of sympathetic-mediated blood pressure Mayer waves in different cardiovascular diseases.
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