title: Captopril treatment and its withdrawal prevents impairment of endothelium-dependent responses in the spontaneously hypertensive rat.
abstract: Angiotensin converting enzyme inhibitors (ACE-I) have been shown to prevent impairment of endothelial cell function in Spontaneous Hypertensive rats (SHR). The purpose of this study was to examine the effects of early, long-term captopril (ACE-I) treatment and its withdrawal on vascular reactivity in SHR. Three groups of male SHR were studied: 1) untreated SHR; 2) SHR treated with captopril in-utero and maintained on oral treatment post-weaning (SHRCAP); and 3) SHR treated with captopril in-utero followed by withdrawal of drug therapy at two months of age (OFFCAP). All rats were studied at six months of age. Isolated aortic ring segments were suspended in tissue chambers for measurement of isometric force. Ring segments were exposed to cumulative concentrations of serotonin or phenylephrine (3 x 10(-9)-3 x 10(-5) M). SHR demonstrated an enhanced sensitivity to serotonin induced contraction. EC50 value were: SHR 3.6+/-1.4 x 10(-7)M, SHRCAP 9.5+/-0.5 x 10(-7) and OFFCAP 8.1+/-0.9 x 10(-7). Endothelium-dependent relaxation to acetylcholine (ACh) was markedly impaired in the SHR. Maximum relaxation (Rmax) to ACh was 61.1+/-1.6% of serotonin induced contraction versus 91.4 +/- 1.2% and 90.7 + 1.8% relaxation in SHRCAP and OFFCAP, respectfully (p<0.05). These data suggest that early, long-term treatment with captopril can prevent alterations in endothelial function observed in SHR even after ACE-inhibitor therapy has been stopped.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham, 35294-0005, USA. akeaton@phybio.bhs.uab.edu
authors.forename: A K
authors.initials: AK
authors.lastname: Keaton
authors.forename: C R
authors.initials: CR
authors.lastname: White
authors.forename: K H
authors.initials: KH
authors.lastname: Berecek
mesh_terms: D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002216:Captopril / Q000009:adverse effects / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006973:Hypertension / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010656:Phenylephrine; D012701:Serotonin; D002216:Captopril