Adipose tissue possesses considerable growth potential, and excess adipose tissue mass is associated with noninsulin dependent diabetes mellitus (NIDDM). Adipose tissue is a significant source of angiotensinogen, the precursor of angiotensin II (All), a vasoactive peptide with in vitro mitogenic effects. The renin‐angiotensin system remains only partially identified in adipose tissue, however, and knowledge of whether All has a physiologic role in this tissue is dependent in part upon other components of the system being characterized. We have chosen to further investigate aspects of the renin‐angiotensin system in separate adipose tissue depots of rats during growth and development of the tissue. Either epididymal or retroperitoneal adipose tissue was examined in young lean, or adult obese male Sprague‐Dawley rats. Adipose tissue was subjected to collagenase digestion, yielding separate vascular and fat cell fractions. Each fraction was analyzed for angiotensin converting enzyme (ACE) activity and All receptor binding capacity. ACE activity was significantly greater when expressed per gram of adipose tissue in the young lean rats. Vascular and fat cell fractions exhibited All receptors of high affinity, with a greater density of receptors observed in the epididymal adipose tissue fractions. Incubation of adipocytes with exogenous All was associated with the release of prostaglandin into the medium, and analyses of adipocyte cytosol indicated the presence of angiotensinogen. Growing rats given oral losartan, an All receptor antagonist, once daily (15 mg/kg) for 2 weeks exhibited reductions in body weight gain, fat mass, fat cell volume, and All receptor number. These data further document the presence of a peripheral renin‐angiotensin system in anatomically distinct adipose tissue depots at different stages of growth. While the characterization of the effects of All upon adipose tissue development remains incomplete, future investigations with agents affecting the adipocyte renin‐angiotensin system could provide additional information on the role of this system in adipose tissue growth.

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To detect the presence in adipose tissue of peptides known to affect tissue growth and to investigate potential regional differences, epididymal and perirenal adipose tissue depots from male Sprague-Dawley rats were separated into adipocyte and stroma-vascular fractions by collagenase digestion, sequential centrifugation and filtration. Identity and integrity of the fractions were demonstrated by light and electron microscopy, while dose-response curves for angiotensin-converting enzyme (ACE) were performed, revealing maintained functional capacity of the stroma-vascular fraction. ACE, atrial natriuretic peptide (ANP), and transforming growth factor-alpha (TGF-alpha) concentrations were significantly greater in epididymal than perirenal stroma-vascular tissue. Adipocyte fractions from both depots contained significant concentrations of ANP and TGF-alpha. There was no detectable ACE in the adipocyte fractions, indicating that no contaminating stromal-vascular cells were present in these fractions. These data show significant concentrations of peptides with effects on growth in subfractions of adipose tissue and demonstrate regional differences in concentrations between fat depots.

1 The effects of noradrenaline (NA) and isoprenaline on isolated atria from aorta-coarcted hypertensive rats (AHR) at early (6 day) and chronic (28 day) stages of hypertension were studied and compared with time-matched, sham-operated, normotensive rats (SNR). The number and affinity of P-adrenoceptors ((-)-[3H]-dihydroalprenolol binding sites) were also studied in cardiac membranes prepared from these animals. 2 Six and 28 days after complete ligation of the abdominal aorta between the two renal arteries, rats became hypertensive with significantly greater arterial blood pressures than time-matched SNR. 3 At both stages of hypertension, the atrial inotropic or chronotropic effects of NA and isoprenaline from hypertensive rats were similar to time-matched SNR. Moreover, no differences in atrial reactivity were observed between the early and chronic stages of hypertension. 4 Irrespective of the stage of hypertension, cardiac membranes from the AHR contained the same number of P-adrenoceptors as time-matched SNR. In addition, the receptor affinity for the radioligand within each group was equivalent. However, the chronic stage hypertensive rats and their time-matched controls contained fewer P-adrenoceptors and these receptors had greater affinity for the radioligand when compared with cardiac membranes from rats at the early stage of hypertension and their controls. 5 The observed equivalent chronotropic and inotropic responses to NA and isoprenaline between the hypertensive and normotensive rats in both stages of hypertension may be explained in terms of similar receptor number and receptor binding affinity. 6 The reduced number of P-adrenoceptors with greater binding affinity in day 28 normotensive or hypertensive rats may be a compensatory mechanism for these animals to maintain normal cardiac function with increasing age.

Captopril (30 mg/kg/day orally for two days) in spontaneously hypertensive rats (SHR) inhibited serum angiotensin converting enzyme (ACE) activity 92.3%; increased plasma renin activity (PRA) 18-fold and reduced mean arterial blood pressure (MABP) 19 mm Hg. Hydrochlorothiazide (HCTZ) (100 mg/kg-day 1; 10 mg/kg-day 2, orally) increased PRA 3-fold but did not affect serum ACE or MABP. HCTZ plus captopril inhibited serum ACE 95.2%; increased PRA 38-fold and reduced MABP 47.5 mm Hg. Captopril or HCTZ plus captopril did not alter the responses of isolated aortic strips to norepinephrine (NE), serotonin, angiotensin II (AII) or isoproterenol. Pressor responses of conscious SHR to AII and NE were unaltered by captopril or HCTZ plus captopril although the bradykinin-induced depressor responses were significantly but equally potentiated. These results suggest that the potentiating effect of HCTZ is due to some mechanism that shifts the animal's blood pressure maintenance system to a renin-dependent state and is not due to changes in vascular reactivity.