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

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 less than 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 less than 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 greater than LBP-SHR greater than SHR greater than 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. 5 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 of the aortae to ACh and histamine. This effect was seen in both the endothelium mediated relaxation and the nonendothelium mediated contraction.