Schlenker, E. H., C. K. Kost, Jr., and M. M. Likness. Effects of long-term captopril and L-arginine treatment on ventilation and blood pressure in obese male SHHF rats. J Appl Physiol 97: 1032-1039, 2004. First published May 14, 2004 10.1152/japplphysiol.00255.2004We investigated the effects of captopril (Cap) and L-arginine (Arg) on hypertension and cardiopulmonary function. Our hypothesis was that Cap therapy or Arg will improve cardiopulmonary risk factors for hypertension and hypoventilation in the obese spontaneously hypertensive heart failure rat, which is characterized by hypertension, obesity, and disorders of lipid and carbohydrate metabolism. For the first study, one group of rats received Cap in drinking water, and a second group received deionized water (DI). For the second study, rats were further subdivided. Some Cap-treated rats continued on this treatment, and the other half were now given DI to determine whether there would be residual effects of Cap treatment. A subgroup of rats who had received DI was then given Arg, whereas the rest remained on DI. In the first study, Cap-treated rats exhibited decreases in systolic and diastolic blood pressures, frequency of breathing, and minute ventilation, but ventilatory control was maintained. In contrast, blood pressures and relative ventilation to metabolism were higher in the DI-treated group. Removal of Cap increased blood pressure and decreased tidal volume while these rats maintained frequency. Although Arg-treated rats did not exhibit a decrease of blood pressure, ventilation was maintained in this group by preserving tidal volume. Thus Cap and Arg affected ventilation through different mechanisms independent of blood pressure.spontaneously hypertensive heart failure rat; hypertension; metabolic syndrome X; ventilatory equivalent; frequency OBESITY, DIABETES, AND HYPERTENSION are major risk factors for cardiopulmonary and renal disease (1,7,9,18,41). The concurrence of these risk factors is also known as the metabolic syndrome X (8, 49). In addition to metabolic and cardiovascular complications, individuals with metabolic syndrome X can also present with hypoventilation during sleep and obstructive sleep apnea (8, 47).Hypertension and congestive heart failure originate from the activation of multiple neuroendocrine systems, including the renin-angiotensin (Ang), endothelin, and atrial natriuretic peptide systems (13, 23-25, 41, 51). One in four adults develops hypertension and is at increased risk of stroke, coronary disease, congestive heart failure, and end-stage renal disease (2). Ang-converting enzyme (ACE) inhibitors are regarded as the first line of hypertensive therapy in diabetic patients due to their protective effects on the cardiovascular and renal systems (23,27,45). Ideally, treatment of hypertension would normalize blood pressure early in the disease, thus decreasing the incidence of cardiovascular-associated morbidity and mortality. Another agent that has been shown to decrease blood pressure is L-arginine (Arg) (50), a substrate ...