Renal and cardiovascular effects of acute and chronic administration of felodipine to SHR

Renal function and salt and water turnover were studied in SHR during acute and chronic administration of felodipine, which is an efficient antihypertensive vasodilating Ca2+ antagonist. In conscious SHR acute administration of felodipine in hypotensive doses increased renal sympathetic nerve activity but caused renal vasodilation, increases in GFR and a 2-3 fold increase in urinary flow rate and sodium excretion. The fraction of filtered sodium excreted (FENa) was approximately doubled. The diuretic and natriuretic effects of felodipine are therefore suggested to be due to a direct inhibitory action on the renal tubular cells, resulting in reduced sodium reabsorption. Nifedipine also induced diuresis and natriuresis in this system, while minoxidil reduced water and sodium excretion. Throughout 6 months of felodipine treatment, the mean arterial pressure (MAP), remained 25-20 per cent reduced. Felodipine in combination with metoprolol reduced MAP 25-30 per cent and also caused regression of left ventricular hypertrophy, while felodipine alone prevented its further progression. Also during chronic administration, felodipine induced diuresis but had no effect on plasma volume and on sodium or potassium excretion in SHR. It is concluded that in SHR felodipine induces diuresis; on acute treatment this is secondary to reduced tubular sodium reabsorption, although during chronic treatment the sodium loss is compensated for while the diuresis remains. Thus, the cardiovascular and renal effects of Ca2+ antagonists like felodipine differ substantially from those of other potent antihypertensive vasodilators e.g. minoxidil.     

Chronic arterial vasodilation, central hemodynamics, and cardiac hypertrophy in spontaneously hypertensive rats.

To determine the possible contribution of cardiac volume overload in the failure of arterial vasodilators to induce regression of left ventricular hypertrophy (LVH), we evaluated in spontaneously hypertensive rats (SHRs) the changes in central hemodynamics caused by treatment with hydralazine or minoxidil. Cardiac output measured by the thermodilution technique and filling pressures were measured in conscious, freely moving rats. Increases in cardiac output were observed after 1 day of treatment, and persisted during chronic treatment; ganglionic blockade did not affect this increase. However, the LV end-diastolic pressure and right atrial pressure of SHRs were not increased by hydralazine or minoxidil. Minoxidil increased the LV weight, and decreased the LV wall thickness to LV internal radius ratio, whereas hydralazine did not change these parameters. We conclude that in SHRs changes in filling pressures do not represent the primary stimulus for the persistence or progression of cardiac hypertrophy during chronic arterial vasodilation.     

Pharmacokinetics of trimazosin and its effects on blood pressure,renal function and proteinuria during short-term therapy of patients with impaired renal function and hypertension

Summary The kinetics and short-term (10 weeks) effects of trimazosin, an alpha₁-adrenoreceptor antagonist, on renal function and blood pressure in patients with moderate chronic renal insufficiency and hypertension, have been studied for the first time. Eight patients in whom the blood pressure was not normalized with a diuretic alone underwent pharmacokinetic studies and assessment of the renal function during a 10-week period of trimazosin therapy. Trimazosin significantly lowered blood pressure (recumbent and upright) without significantly altering renal function. Renal vascular resistance was decreased by 14%. Fractional sodium excretion, proteinuria and laboratory serum tests remained unchanged. Neither body weight nor pulse rate were affected. Moderate renal insufficiency did not modify the pharmacokinetics of the drug. Thus, trimazosin, as second-step antihypertensive agent, appeared to be safe and effective in patients with moderate renal insufficiency and hypertension, without exerting favourable or adverse renal effects during short-term therapy.     

Evaluation of minoxidil

The chemistry, pharmacokinetics, mechanism of action, clinical studies, adverse effects, toxicology, indications, contraindications, drug interactions, and dosing of minoxidil, a recently approved antihypertensive agent, are reviewed. Minoxidil is an orally effective vasodilator that selectively relaxes peripheral arteriolar smooth muscle, Reflex tachycardia, renin stimulation, and sodium retention occur when minoxidil is used and so it requires the concomitant use of a diuretic and a sympathoplegic agent, usually a beta blocker. Hirsutism and pericardial effusions are additional adverse effects. Minoxidil is indicated in the management of severe hypertension in patients who do not respond to standard antihypertensive agents. In controlled and unctrolled studies, minoxidil was effective in patients with hypertension secondary to renal or renovascular disease and in patients with essential hypertension. Minoxidil is a potent antihypertensive agent with adverse effects that limit its use to patients resistant or intolerant to other drugs.     

Pruritic rash with actinic keratosis and impending exfoliation in a patient with hypertension managed with minoxidil

Dermatological toxicity has been reported following initiation of therapy with minoxidil, but no cases have been reported following prolonged use. We report the emergence of an erythematous weeping rash with impending exfoliation three years after the initiation of minoxidil therapy. Minoxidil was withdrawn and the patient responded to therapy with topical corticosteroids. Following minor surgery, the patient was inadvertently rechallenged with minoxidil. Within 24 hours of exposure bullous lesions reappeared in the extremities which again resolved with topical corticosteroids. Dermatological lesions observed on this patient were similar to those reported following acute minoxidil exposure and strongly implicate chronic minoxidil therapy.     

The pharmacokinetics of 2.5- to 10-mg oral doses of minoxidil in healthy volunteers

The dose proportionality of minoxidil was investigated by studying its pharmacokinetics after administration of single, oral doses of 2.5, 5.0, and 10.0 mg. The study, which was a Latin square cross-over design, was performed in 30 young, nonobese, normal subjects. Treatments were separated by a 4-day washout period. Serum and urine levels of minoxidil were determined by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Supine blood pressure and pulse were monitored during each study phase. Minoxidil concentrations determined by RIA were highly correlated with concentrations determined by HPLC; only the HPLC data was used in the pharmacokinetic analyses. No significant effects were observed for dose normalized Cmax, tmax, volume of distribution, minoxidil renal clearance, or the percentage of the dose excreted as either minoxidil or minoxidil glucuronide. Significant differences in apparent oral clearance, dose normalized AUC, and terminal elimination rate constant (beta) were observed between the 2.5-mg dose and the higher doses, but no differences in these parameters between the 5.0- and 10.0-mg doses were apparent. Thus, the available data support dose-independent pharmacokinetics for minoxidil over this range of doses. Repeated measures analysis of variance detected significant time and treatment effects on supine blood pressure and pulse rate, but the effects were generally small and of little clinical significance. The results support the hypothesis that minoxidil has little effect on blood pressure in normotensive subjects.     

Disposition of minoxidil in patients with various degrees of renal function

The disposition of minoxidil was evaluated after a 5 mg oral dose in 24 subjects with various degrees of renal function. Patients were divided into four groups based on a 24-hour ambulatory creatinine clearance (Clcr): Group I (n = 6) Clcr greater than 90 mL/min, Group II (n = 6) Clcr 50-80 mL/min, Group III (n = 5) Clcr of 30-49 mL/min, and Group IV (n = 7) Clcr less than 30 mL/min. Blood and urine samples obtained over 36 hours were analyzed for minoxidil by a high pressure liquid chromatography technique. Maximum plasma concentration (Cmax) and time to reach Cmax did not differ among the four groups. The terminal elimination half-life was prolonged in Group IV subjects (8.87 +/- 6.12 hours) (mean +/- SD) compared to those in Groups I, II and III (1.38 +/- 0.16, 1.99 +/- 0.45 and 2.42 +/- 0.53 hours, respectively). Apparent total body clearance (Clp/F) decreased as renal function declined; Clp/F = 0.82(Clcr) + 21.8, r = 0.739, P = 0.0001. Renal clearance and apparent nonrenal clearance also were significantly correlated with Clcr. The apparent volume of distribution significantly increased as renal function declined. Thus, the disposition of minoxidil is significantly delayed and dosage adjustment may be necessary in patients with renal insufficiency.     

Atypical effect of minoxidil sulphate on guinea pig airways

The effects of minoxidil sulphate, an "atypical" K(ATP) channel opener, and bimakalim, a benzopyran-type classical K(ATP) channel opener, on guinea pig airways in vitro and in vivo and on isolated portal veins from rats and guinea pigs were compared. Minoxidil sulphate inhibited the spontaneous activity of isolated guinea pig and rat portal vein preparations with pD2 values of 7.83+/-0.08 and 7.14+/-0.03, respectively (Emax=100% in both preparations). Bimakalim caused a more potent inhibition with pD2 values of 8.80+/-0.05 and 8.20+/-0.04, respectively (Emax=100% in both preparations). Minoxidil sulphate reduced the spontaneous tone of isolated guinea pig tracheal rings with a pIC50 value of 3.92+/-0.02 and the same efficacy as isoprenaline. Bimakalim was more potent (pIC50=7.25+/-0.02) but less efficacious (Emax=75% of the Emax of isoprenaline). The airway relaxant effect of bimakalim, but not minoxidil sulphate, was antagonised by glibenclamide (pA2=7.50) at concentrations above 0.1 microM. Bombesin-induced bronchoconstriction in anaesthetised, ventilated, normoreactive guinea pigs (measured as increase in total lung resistance) was dose-dependently reversed by intratracheally (i.t.) administered bimakalim (ED50=4 microg/kg; Emax=92% of maximally possible inhibition), but not by minoxidil sulphate, at doses up to 1 mg/kg i.t. In the same animals, following i.t. administration of higher doses, both minoxidil sulphate and bimakalim reduced blood pressure. Airways hyperreactivity to histamine induced by acute treatment of guinea pigs with immune complex was dose-dependently reversed by bimakalim (ED50=0.5 microg/kg i.t., Emax=100%). This effect was antagonised by glibenclamide (30 mg/kg i.v.). Minoxidil sulphate had a biphasic effect on airways hyperreactivity: at 1 microg/kg i.t., airways hyperreactivity was augmented, whereas at doses above 3.2 microg/kg i.t. it caused reversal of airways hyperreactivity. Both of the effects of minoxidil sulphate were insensitive to glibenclamide (30 mg/kg i.v.). It is concluded that the pharmacological profile of minoxidil sulphate in guinea pig airways is completely different from that of classical K(ATP) channel openers such as bimakalim. Minoxidil sulphate is either only weakly active or even inactive at K(ATP) channels in guinea pig airways or interacts with these channels in a different manner. The current results are consistent with there being differences between the K(ATP) channels in airways and blood vessels.     

Metabolism of minoxidil, a new hypotensive agent I: absorption, distribution, and excretion following administration to rats, dogs, and monkeys.

Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide), a potent new hypotensive agent, was 14C-labeled in the 2-position of the pyrimidine ring in 17 percent yield from Ba14CO3. This material was used to study the absorption, distribution, and excretion of the drug in rats, dogs, and monkeys. Following oral administration of a single dose, the drug was rapidly and well absorbed and rapidly eliminated by each species as judged by plasma levels and urinary excretion of unchanged drug and total drug-related materials. Chronic oral administration of the drug at a high level (10 mg/kg) for 30 days slightly increased the rate of clearance of minoxidil and minoxidil-related material from circulation. Water diuresis, resulting from water loading of dogs, caused an even greater increase in the rates of disappearance of the drug and drug-related material. Whole-body autoradiography studies in rats showed that minoxidil was rapidly distributed following its oral and intravenous administration. It was subsequently concentrated, primarily in the excretory system. Minoxidil-related material was detected in aorta walls, but not in the CNS, following both routes of drug administration.     

Minoxidil does not possess androgenic activity

Minoxidil is a potent antihypertensive vasodilator. One of the side effects of minoxidil is hirsutism. Therefore the hypothesis was tested whether minoxidil has androgenic effects. The weights of seminal mice vesicles, organs with a high sensitivity to androgens, are widely used as a sensitive bioassay for testing androgenic activity. Our results demonstrated that minoxidil in relatively high doses did not produce any significant changes in the weight of seminal vesicles of castrated mice. We conclude that minoxidil in this experimental model does not have any androgenic properties.     

Comparison of the effects of several potassium-channel openers on rat bladder and rat portal vein in vitro.

1. The ability of several K-channel openers to inhibit KCl-induced contractions of rat bladder detrusor and spontaneous mechanical activity in rat portal vein was examined. 2. Lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 dose-dependently relaxed rat detrusor, precontracted with 20 mM KCl. With the exception of pinacidil, concentrations of these agents below 30 microM did not inhibit 80 mM KCl-included contractions. Pinacidil (10 microM) produced a small, but significant (P < 0.05) relaxation of 80 mM KCl-induced mechanical activity. Minoxidil sulphate and BRL 38226 produced some relaxation of 20 mM but not 80 mM KCl-induced contractions. 3. Glibenclamide (0.3-3 microM) antagonized the relaxant effects of lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 in a competitive manner (pA2 values 6.3-6.6). The effects of minoxidil sulphate and BRL 38226 were fully antagonized by 3 microM glibenclamide. 4. Lemakalim, pinacidil, S 0121, BRL 38226 and minoxidil sulphate were each approximately 8 times more potent as inhibitors of the spontaneous contractions of rat portal vein than KCl-induced contractions of the rat detrusor. Minoxidil sulphate was approximately 30 times more potent in the rat portal vein than in the bladder. This may indicate that either minoxidil sulphate is acting at different recognition sites in these two tissues, or that this compound has an additional mechanism of action in the portal vein. 5. With the exception of minoxidil sulphate, all the compounds tested stimulated 86Rb efflux and 42K efflux from preloaded rat detrusor strips.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of oral penbutolol on renal haemodynamics of hypertensive patients with renal insufficiency

Acute or chronic administration of most beta-adrenoreceptor blocking drugs is associated with a fall in renal blood flow and glomerular filtration rate. In patients with renal insufficiency this effect on renal function may be clinically important. Penbutolol is a non-cardioselective, pure laevo, beta-blocker with intrinsic sympathomimetic activity. Previous studies have suggested that penbutolol may increase the glomerular filtration rate. In this study eight hypertensive patients with renal insufficiency were studied during a three-week placebo period and then for four weeks while taking penbutolol in a dose of 40 or 80 mg daily. Penbutolol produced a fall in the pulse rate in all eight patients. Five of the eight patients had a fall in their supine and standing blood pressure. Effective renal plasma flow and glomerular filtration rate did not change significantly. In seven of the eight patients there was a fall in the calculated renal vascular resistance but the mean fall did not reach statistical significance. Penbutolol appears to be an effective beta-blocker and one that could be used appropriately in patients with renal insufficiency.     

Effect of nitric oxide synthesis modification on renal function in gentamicin-induced nephrotoxicity

We evaluated the effect of acute or chronic nitric oxide (NO) synthesis activation or inhibition in rats with gentamicin-induced acute renal failure. Rats received gentamicin 100 mg/kg per day for 6 days, or isotonic saline. Some animals of each group also received N(G)-monomethyl-l-arginine (l-NAME, 4 mg/kg per day) or l-arginine (1%) in the drinking water for 6 days (chronic NO synthesis modification). In another experimental set, animals were treated with gentamicin or saline for 6 days and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured before and after the infusion of l-NAME (50 mg/h per kg) or l-arginine (60 mg/h per kg) (acute NO synthesis modification). Acute l-NAME administration induced a decrease in GFR and RPF both in control and gentamicin treated animals. Chronic l-NAME treatment induced an impairment in GFR only in gentamicin-treated animals. Acute l-arginine administration did not modify renal function in any experimental group whereas chronic l-arginine administration improved renal function only in gentamicin-treated animals. Urinary excretion of N-acetyl-β-d-glucosaminidase and alkaline phosphatase was increased by chronic treatment with l-NAME in both groups, whereas l-arginine had no effect. In conclusion, NO synthesis inhibition aggravates gentamicin-induced renal damage. However, chronic NO synthesis stimulation partially prevents against gentamicin nephrotoxicity, thus suggesting that increased renal NO synthesis during gentamicin-induced nephrotoxicity plays a protector role on renal function.     

Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.

1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed.     

重症感染肿瘤患者使用万古霉素致相关肾功能不全的危险因素分析

目的:统计分析肿瘤患者使用万古霉素治疗重症感染致肾功能不全的发生率及相关危险因素。方法:回顾我院24个月共87例入住重症监护病房的重症感染肿瘤患者使用万古霉素的病历,采集包括合并慢性疾病情况、合并肾毒性药物情况、用药前肿瘤治疗情况(是否手术、放疗、化疗)及急性生理与慢性健康评分(APACHE-Ⅱ评分)等数据,详细记录万古霉素的剂量、疗程及用药前后血肌酐水平等。使用SPSS 21.0统计学软件,进行单变量及多变量分析(χ²检验, P<0.05定义为差异有统计学意义)。结果:纳入病例中57例(65.5%)患者APACHE-Ⅱ评分在15分以上,24例(27.6%)患者合并慢性疾病(高血压、糖尿病、慢性阻塞性肺疾病等),34例(39.1%)患者万古霉素使用疗程在7 d以上,50例(57.5%)患者用药前30 d内行手术治疗,13例(14.9%)患者用药前30 d内行放射治疗,23例(26.4%)患者用药前30 d内行肿瘤化疗。18例(20.7%)患者在使用万古霉素后至停药14 d内出现不同程度的肾功能不全。单变量分析显示年龄、性别、合并慢性疾病情况、药物使用疗程、用药前手术、放疗、用药前血肌酐水平及合用潜在肾毒性药物情况对用药后肾功能不全的发生无显著影响。APACHE-Ⅱ评分、用药前30 d内行肿瘤化疗对用药后肾功能不全发生率有显著影响(P=0.034、P=0.011)。结论:APACHE-Ⅱ评分较高及用药前30 d曾行化疗的肿瘤患者在发生重症感染使用万古霉素时发生肾功能不全的风险增加,应特别注意。     

Nongenotoxicity of minoxidil in murine hair follicles as determined by the nuclear aberration assay

A 1-cm2 area on the back of CD1 mice was prepared for topical application of minoxidil, N-methyl-N-nitrosourea (MNU), or cyclophosphamide (CY) by clipping or plucking hair from a patch of skin. Plucking stimulates hair follicle cell division while clipping does not. Minoxidil was topically administered for 8 consecutive days. CY or MNU was administered topically once on the eighth day postplucking. The incidence of nuclear aberrations and mitotic figures were measured in hair follicles while frequency of micronuclei and the ratio of RBC/PCE were measured in the bone marrow. Results with minoxidil showed no increase in either nuclear aberrations in the hair follicle or micronuclei in the bone marrow. These results suggest that topically applied minoxidil is not genotoxic. In contrast, a dose-dependent effect of MNU on the incidence of nuclear aberrations in the hair follicle was seen. CY induced a dose-dependent increase in the incidence of micronuclei in the bone marrow and in nuclear aberrations in the hair follicle after topical application. Minoxidil applied to clipped mice significantly increased the incidence of mitotic figures above that seen in both the clipped and plucked controls. This suggests that minoxidil is a mitogenic agent in the hair follicle. These findings are consistent with the success of topically applied minoxidil in the treatment of alopecia areata.     

米诺地尔联合地塞米松对肾缺血再灌注损伤大鼠肾功能指标和氧化应激指标的影响

目的探究米诺地尔联合地塞米松对肾缺血再灌注损伤大鼠肾功能指标和氧化应激指标的影响。方法 40只SD大鼠通过ip 1%戊巴比妥钠溶液4 mg/kg建立肾缺血再灌注损伤模型,分为假手术组、模型组、地塞米松组、米诺地尔组、米诺地尔联合地塞米松组,每组8只。假手术组不进行肾缺血再灌注处理;模型组术前30 min ip生理盐水1 mL;地塞米松组术前30 min ip 4 mg/kg地塞米松磷酸钠注射液;米诺地尔组术前30 min ip 0.6 mg/kg米诺地尔;米诺地尔联合地塞米松组术前30 min ip 0.3 mg/kg米诺地尔和2 mg/kg地塞米松磷酸钠注射液。考察米诺地尔联合地塞米松对肾缺血再灌注损伤大鼠肾功能指标和氧化应激指标的影响。结果地塞米松组、米诺地尔组、米诺地尔联合地塞米松组的血清尿素氮(BUN)、肌酐(Cr)值和肾组织丙二醛(MDA)值均显著低于模型组(P0.05、0.01),以米诺地尔联合地塞米松组最为显著(P0.01);肾组织匀浆总超氧化物歧化酶(T-SOD)活性均显著高于模型组(P0.01),以米诺地尔联合地塞米松组最为显著(P0.01)。结论地塞米松和米诺地尔预处理均可以显著减轻急性肾缺血再灌注的损伤,且两者对急性肾缺血再灌注损伤的保护作用总体相近,联合用药预处理的保护作用则更加显著。     

米诺地尔酊的制备及质量控制

目的 制备来诺地尔酊并对其质量进行研究.方法 以米诺地尔为主药制备酊剂剂;对米诺地尔酊进行性状、鉴别、乙醇量、丙二醇量、有关物质、含量测定等质量研究;结果 该制剂为无色或微黄色的澄清液体;其它各项质量指标均符合药典,利用高效液相色谱法测定制剂含量准确可靠.结论 该制剂处方工艺简便可行,质量可控.     

Acute and chronic effects of a new calcium inhibitor, nicardipine, on renal hemodynamics in hypertension

Renal hemodynamics and natriuresis were studied in 10 hypertensive patients without renal failure, 2 and 4 h after oral intake of 30 mg nicardipine; then, nicardipine was given at a dose of 30 mg three times a day and the hemodynamic study was repeated on the 6th day (2 h after the morning dose). The first dose of nicardipine produced an increase in renal blood flow (from 888 +/- 45 to 999 +/- 59 ml/min 1.73 m2, p less than 0.01) and a decrease in renal vascular resistances (from 0.16 +/- 0.01 to 0.12 +/- 0.01 arbitrary unit, p less than 0.05). Glomerular filtration rate did not change and the decrease in filtration fraction was not significant. Sodium excretion increased markedly during the first 2 h (from 0.17 +/- 0.04 to 0.29 +/- 0.06 mmol/min, p less than 0.05). On the 6th day renal vascular resistances and filtration fraction remained lowered whereas glomerular filtration rate was unchanged. Nicardipine did not produce any significant alteration in plasma renin activity and plasma aldosterone after acute or chronic administration. These results confirm the potent renal vasodilatory effect of nicardipine; glomerular filtration rate was not significantly altered whereas renal blood flow and filtration fraction returned to normal levels. An early and transient natriuretic effect was observed after the first dose of nicardipine, and body weight showed a significant decrease during the study indicating that no sodium retention was induced by nicardipine.     

Effects of minoxidil on ischemia-induced mechanical and metabolic dysfunction in dog myocardium

Effects of minoxidil on ischemia-induced myocardial mechanical and metabolic dysfunction were examined in anesthetized open-chest dogs. A regional portion of the left ventricle was made ischemic for 20 min by ligating the left anterior descending coronary artery, and then reperfused for 120 min. Dimethylsulfoxide or minoxidil (0.3, or 1.0 mg/kg) was injected intravenously 10 min before ligation. Ischemia decreased regional myocardial contraction, and reperfusion recovered it but incompletely. Myocardial metabolic derangement was observed during ischemia, such as decreases in the myocardial levels of ATP and creatine phosphate. These metabolic changes caused by ischemia were restored by reperfusion. Minoxidil injection at 0.3 and 1.0 mg/kg significantly decreased blood pressures but increased coronary flow. Pretreatment with minoxidil significantly enhanced the recovery of myocardial contraction during reperfusion after ischemia. The levels of ATP and creatine phosphate in the ischemic myocardium were significantly preserved by minoxidil at 0.3 mg/kg. No significant effect of minoxidil on the metabolism was observed in the 120 min reperfused myocardium. In conclusion, minoxidil improved the mechanical dysfunction in the reperfused heart and the drug at low dose preserved high-energy phosphates during ischemia.