Decreased responsiveness of the aortae of hypertensive rats to acetylcholine, histamine and noradrenaline

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Abstract
The responses to noradrenaline (NA) of the aortae of various hypertensive rats, namely the spontaneously hypertensive rat (SHR), the low blood pressure SHR (LBP-SHR), and the left renal artery stenosed LBP-SHR (LRAS-LBR-SHR), were compared to those of the normotensive Wistar-Kyoto rats (WKY). The aortae of the hypertensive rats were significantly more responsive (P < 0.05) to 10-8 M NA. However, the reverse was true for higher doses of NA. The ED50 values for the aortae of WKY, LBP-SHR, SHR and LRAS-LBP-SHR were 20, 8.5, 7.8 and 8 nM respectively. The NA-contracted aortae of the LRAS-LBP-SHR were significantly less responsive (P < 0.05) to the relaxant action of histamine and acetylcholine (ACh) compared to those of the WKY. This observation was not made in the aortae of the LBP-SHR. The maximal relaxation (% of the maximal contraction induced by 10-8 M NA) observed in the aortae of WKY, LBP-SHR and LRAS-LBP-SHR were, respectively, 72 .+-. 2, 66 .+-. 6, 39 .+-. 7 for ACh and 50 .+-. 3, 36 .+-. 4, 27 .+-. 3 for histamine. In aortae where the endothelium had been removed by collagenase treatment, histamine induced a dose-related contraction. The rank order of this dose-related contraction was WKY > LBP-SHR > SHR > LRAS-LBP-SHR with the corresponding maximal tension (g) 0.89 .+-. 0.04, 0.59 .+-. 0.04, 0.36 .+-. 0.04, 0.19 .+-. 0.05. The results suggested that elevation of blood pressure above the normal (due either to intrinsic or extrinsic factors), as seen in SHR and LRAS-LBP-SHR, results in a decreased response to the aortae to ACh and histamine. This effect was seen in both the endothelium mediated relaxation and the non-endothelium mediated contraction.