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Comparative haemodynamic studies of endothelin-1, -2 and -3 on conscious SHRSP and WKY
H Higashino1, K Simeonova, I Lambev
1Department of Pharmacology, Kinki University School of Medicine, Osaka, Japan.
Insights
Endothelin peptides did not significantly alter blood pressure in WKY and SHRSP rats, suggesting they do not play a major role in hypertension development. However, Endothelin-1 demonstrated potent vasodepressor effects and induced cardiac arrhythmia.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Endothelin Signaling
Background:
- Endothelins (ETs) are potent vasoactive peptides implicated in cardiovascular regulation.
- Their role in the pathogenesis of hypertension, particularly in different rat models, requires further elucidation.
Purpose of the Study:
- To investigate the depressor and pressor effects of endothelin-1, -2, and -3 in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive stroke-prone (SHRSP) rats.
- To assess the potential involvement of endothelins in the development of hypertension.
Main Methods:
- Administration of three doses of endothelin-1, -2, or -3 (0.1, 0.3, and 1 nmol/kg) to conscious WKY and SHRSP rats.
- Measurement of systolic arterial pressure, cardiac index, and observation for cardiac arrhythmia.
Main Results:
- Systolic arterial pressure changes (depressor and pressor responses) to endothelins were similar in WKY and SHRSP rats.
- Endothelin-1 exhibited the most potent vasodepressor and vasodilator activity among the tested peptides.
- Endothelin-1 caused a greater decrease in cardiac index in SHRSP than WKY rats, suggesting ETA receptor dominance in SHRSP.
- Cardiac arrhythmia was frequently observed during pressor responses to endothelin-1 and -3 in both rat groups.
Conclusions:
- Endothelins may not play a significant role in the pathogenesis of hypertension.
- Endothelin-1 is a potent vasodepressor and vasodilator in rats.
- Endothelin peptides possess arrhythmogenic properties and may act via ETA receptors in SHRSP rats.
Abstract:
1. Depressor and pressor effects of endothelin-1, -2 and -3 in relation to hypertension were investigated in conscious WKY and SHRSP. 2. Changes of systolic arterial pressure to both depressor and pressor responses caused by three doses of endothelin-1, -2 or -3 (0.1, 0.3 and 1 nmol/kg) occurred to a similar extent between WKY and SHRSP. These data showed that endothelins may not exert an important role on the pathogenesis of hypertension. 3. Endothelin-1 decreased the cardiac index more in SHRSP than in WKY, indicating the dominance of ETA receptors in SHRSP compared with WKY. 4. ET-1 was the most potent vasodepressor and vasodilator of three endothelin peptides in rats. 5. During the pressor responses to endothelin-1 and -3, cardiac arrhythmia was observed with high frequency in the animals of both groups, indicating the arrhythmogenic effect of ET.