Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril.

We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30% change in <10 days). Despite changes in LV mass, specific activities of bioenergetic (cytochrome-c oxidase, citrate synthase, lactate dehydrogenase) and reactive oxygen species (ROS) (total cellular superoxide dismutase) enzymes were actively maintained within relatively narrow ranges regardless of treatment duration, organismal age, or transmural region. Although enalapril led to parallel declines in mitochondrial enzyme content and ventricular mass, total ventricular mtDNA content was unaffected. Altered enzymatic content occurred without significant changes in relevant mRNA and protein levels. Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2alpha) were also unchanged. In contrast, enalapril-mediated ventricular and mitochondrial remodeling was accompanied by a twofold increase in specific activity of catalase, an indicator of oxidative stress, suggesting that rapid cardiac adaptation is accompanied by tight regulation of mitochondrial enzyme activities and increased ROS production.

Recovery of erectile function after brief aggressive antihypertensive therapy.

PURPOSE: We have previously demonstrated that antihypertensive therapy could structurally modulate blood vessels in the penis, although the impact on erectile function was not established. Given the importance of inadequate penile arterial inflow as a cause of erectile dysfunction we determined in spontaneously hypertensive rats the impact of brief aggressive antihypertensive therapy on structurally based penile vascular resistance, erectile function and mean arterial pressure during and after treatment. MATERIALS AND METHODS: Young (15-week-old) and aged (40-week-old) spontaneously hypertensive rats were treated for 2 weeks (enalapril 30 mg./kg. daily plus a low salt diet). Mean arterial pressure was continuously monitored via radio telemetry. Erectile responses were assessed by administering apomorphine (80 microg./kg. subcutaneously) before, during and after treatment. Structurally based vascular resistance was determined in the isolated, perfused penile vasculature 2 weeks after stopping treatment in aged spontaneously hypertensive rats. Certain responses were determined, including resistance at maximum dilatation (lumen size) and at maximum constriction (medial bulk), and EC50 of the alpha-adrenoceptor agonist methoxamine. RESULTS: In the period after the cessation of drug treatment there was a persistent reduction in the level of arterial pressure (16%) and a doubling of erectile responses compared with pre- treatment. Cardiac and vascular structure regressed, as determined by the mean decrease plus or minus standard deviation in vascular resistance at maximum dilatation (21% +/- 4.5%) and mean reduction in left ventricle mass (10.4% +/- 3.7%). Furthermore, treatment induced a significant right shift in alpha1-adrenoceptor concentration response curve in treated versus control rats (mean EC50 1.09 +/- 0.111 versus 0.76 +/- 0.111). CONCLUSIONS: The improvement in erectile function after brief aggressive treatment may be related to improvement in structurally based vascular resistance within the penis and the decrease in responsiveness of alpha1-adrenoceptor mediated erectolytic signaling. These findings are suggestive of a new therapeutic strategy for hypertension and erectile dysfunction.

Chemical stability of meperidine hydrochloride in polypropylene syringes.

The physical and chemical stability of preservative-free meperidine hydrochloride solutions in polypropylene syringes was studied. Solutions of meperidine hydrochloride were diluted in dextrose 5% and normal saline to 0.25, 1, 10, 20, and 30mg/mL, repectively, and stored at either 22 deg C or 4 deg C for 28 days. All solutions were protected from light druing storage. Triplicate samples were taken from each syringe on days zero, one, three, seven, 14 and 28 and frozen at -72 deg C. Samples were analyzed in duplicate using a stability-indiicating high-pressure liquid chromatography assay. All samples remained colorless and free of precipitate throughout the course of the study. The concentration of meperidine remaining after the 28-day storage period was greater than 90% of the initial concentration for all the concentrations, diluents and temperatures studied.