Abstract
The effect of hypertension and acute (36-h) or chronic (from age 6 to 16 weeks) antihypertensive treatment with prazosin (2 mg kg-1 per day), nifedipine (50 mg kg-1 per day), or captopril (50 mg kg-1 per day) on Ca2+ mobilization due to α1-adrenoceptor activation was analyzed in functional studies using arterial rings [four conductance/distributing vessels: aorta, main mesenteric, iliac, and tail arteries and two resistance vessels; first and second small mesenteric artery branches obtained from spontaneously hypertensive rats (SHR, 6 and 16 weeks old) and age-matched Wistar Kyoto rats (WKY)]. Maximal response to noradrenaline in the presence of extracellular Ca2+ is not affected by hypertension or by the antihypertensive treatment. The extracellular Ca2+-independent contractile responses increased with age in iliac, tail, and small mesenteric arteries (SMA) and were further increased in SHR in SMA from both young and adult animals and in the main mesenteric artery of adult SHR. In main mesenteric artery, this increased contraction in SHR was associated with a higher increase in cytosolic [Ca2+] mobilized by noradrenaline without changes in the total stored Ca2+. Acute or chronic treatment with captopril abolished the differences observed between WKY and SHR in the noradrenaline-induced contraction in mesenteric arteries loaded in Ca2+-free medium. In contrast, animals acutely treated with prazosin or chronically treated with either prazosin or nifedipine exhibit the same differences in Ca2+ handling than untreated rats. In conclusion, these differences are not a consequence of increased blood pressure but precede it and can only be normalized by inhibition of the rennin-angiotensin system.
Footnotes
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This study was supported by a research grant from the Spanish Comisión Interministerial de Ciencia y Tecnología (SAF2001-2656). Part of this work has been previously presented at the 3rd Meeting of the Federation of the European Pharmacological Societies (EPHAR), July 2001; XXV Congress of the Spanish Society of Pharmacology, October 2003; and XXVI Congress of the Spanish Society of Pharmacology, September 2004.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.104.078725.
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ABBREVIATIONS: SHR, spontaneously hypertensive rat(s); WKY, Wistar Kyoto rat(s); SMA, small mesenteric arteries; SMA-1, first branch of small mesenteric artery; SMA-2, second branch of small mesenteric artery; SBP, systolic blood pressure; NA, noradrenaline.
- Received October 5, 2004.
- Accepted December 16, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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