Captopril--Possible Use

[DrJMW]

This article explains the role of angiotensin II in the formation of adipose tissue. Read it and extrapolate this idea: What happens to adipose tissue if we can inhibit angiotensin II formation (which is what Captopril does)?





Angiotensinogen, angiotensin II and adipose tissue development.
Int J Obes Relat Metab Disord 2000 Nov;24 Suppl 4:S33-5 (ISSN: 0307-0565)
Ailhaud G; Fukamizu A; Massiera F; Negrel R; Saint-Marc P; Teboul M
Laboratoire Biologie du Developpement du Tissu Adipeux, Centre de Biochimie (UMR 6543 CNRS), UNSA, Nice, France. [email protected].
Adipose tissue is an important source of angiotensinogen (AGT). Recent evidence shows that a local renin-angiotensinogen system (RAS) is present in human adipose tissue and may act as a distinct system from plasma RAS. In obese patients, the involvement of angiotensin II (angII) as a consequence of increased plasma AGT secreted from adipose tissue has been proposed in the development of hypertension. Another role of AGT via angII in the development of adipose tissue is supported by the following: (i) in vitro, angII stimulates the production and release of prostacyclin from adipocytes, which in turn promotes the differentiation of precursor cells into adipocytes; (ii) ex vivo and in vivo, both angII and (carba)prostacyclin promote the formation of new fat cells; and (iii) AGT -/- mice exhibit a slowing down of adipose tissue development, as compared to wild-type mice. Altogether the data are consistent with an autocrine/paracrine mechanism implicating AGT, angII and prostacyclin in adipose tissue development.

 

[nandi12]

Thanks for posting that. Some of the other stuff that has been posted about captopril "eliminating" alpha 2 receptors just did not seem to be in accord with any research, except for a couple of papers dealing with the downregulation of those receptors in platelets.

 

[nandi12]

Dr. JMW, that post gave me a good starting point for a Medline search that revealed tons of research on this subject. I just started to skim the abstracts and was immediately struck by these. ACE inhibitors seem to do nothing, and theoretically might backfire:

Diabetes 2002 Jun;51(6):1699-707 Related Articles, Books, LinkOut


Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors.

Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM.

Max Delbruck Center for Molecular Medicine, HELIOS Klinikum-Berlin, Franz Volhard Clinic, Medical Faculty of the Charite, Humboldt University of Berlin, Berlin, Germany.

Recent studies suggest that angiotensin II (Ang II) plays a role in the adipogenesis of murine preadipocytes. Here, we examined the role of Ang II for the differentiation of primary cultured human preadipocytes. Preadipocytes were isolated from human adipose tissue and stimulated to differentiate. Quantitation of gene expression during adipogenesis was performed for renin-angiotensin system (RAS) genes. The influence of the RAS on adipogenic differentiation was investigated by addition of either angiotensinogen (AGT), Ang II, or angiotensin receptor antagonists to the differentiation medium. We also examined the influence of adipocytes on adipogenesis by co-culture experiments. Expression of the RAS genes AGT, renin, angiotensin-converting enzyme, and Ang II type 1 receptor increased during adipogenesis. Stimulation of the Ang II type 1 receptor by Ang II reduced adipose conversion, whereas blockade of this receptor markedly enhanced adipogenesis. Adipocytes were able to inhibit preadipocyte differentiation in the co-culture, and this effect was abolished by blockade of the Ang II type 1 receptor. This finding points to a functional role of the RAS in the differentiation of human adipose tissue. Because AGT secretion and Ang II generation are characteristic features of adipogenesis, we postulate a paracrine negative-feedback loop that inhibits further recruitment of preadipocytes by maturing adipocytes.

Metabolism 2001 Apr;50(4):468-72

The effects of angiotensin-II on lipolysis in humans.

Townsend RR.

Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.

Adipocytes express many of the proteins of the renin-angiotensin system including angiotensinogen and AT(1)-receptors. A principal function of adipocyte tissue is the provision of energy substrate through lipolysis. This study was undertaken to determine if angiotensin-II (Ang-II) infusion or blockade of the renin-angiotensin system by angiotensin-converting enzyme (ACE) inhibitor therapy with enalapril altered lipolytic activity and substrate oxidation. Eleven healthy male subjects were enrolled in the first study and postabsorptive whole-body lipolysis activity was measured using a stable isotope of glycerol ((2)H(5)-glycerol). Substrate oxidation was determined using indirect calorimetry in the Clinical Research Center. Subjects were then sequentially treated with low-dose Ang-II infusion (0.3 and then 1.0 ng/kg/min) on separate days, and the lipolysis and oxidation studies were repeated. Lastly, each subject was treated with 2 weeks of ACE inhibitor with enalapril (20 mg daily) and underwent lipolysis and oxidation studies for a fourth time. In a second study, 14 healthy male subjects were enrolled and underwent an identical baseline lipolysis and substrate oxidation assessment. These subjects then received an Ang-II infusion at pressor doses (10 ng/kg/min), and changes in lipolytic activity and substrate oxidation were measured again. In the first study, there was no effect on lipolysis activity from low-dose Ang-II infusion (baseline lipolysis activity (mean +/- SD) 2.06 +/- 0.55 micromol/kg/min, 2.10 +/- 0.69 micromol/kg/min after 0.3 ng/kg/min, and 2.32 +/- 0.56 micromol/kg/min after 1.0 ng/kg/min) or enalapril therapy (2.35 +/- 1.00 micromol/kg/min). In the second study, the larger dose of Ang-II increased blood pressure by 14/17 mm Hg, but there was no effect on lipolysis activity (1.36 +/- 0.49 micromol/kg/min v 1.63 +/- 0.82 micromol/kg/min). Substrate oxidation rates were largely unaffected by Ang-II infusions or enalapril therapy. There was no evidence that treatment with subpressor or pressor dosages of Ang-II produced a significant alteration in lipolytic activity. Moreover, blockade of the renin-angiotensin system with enalapril was equally unremarkable in its effects on whole-body lipolysis. These data support the general concept that the renin-angiotensin system in adipocytes serves more to regulate the regional blood flow to adipose tissue and the size and number of fat cells rather than participating directly in the regulation of energy substrate. Copyright 2001 by W.B. Saunders Company

 

[DrJMW]

Good read. Seems there is a conflict among researchers. It will be interesting to see how it plays out. I couldn't find any articles showing HGH and Captopril interaction. Remember, I mentioned that Captopril is only one component of the stack (HGH, Captopril, Yohimburn)--it isn't a stand-alone miracle drug. If the contrary research turns out to be correct, then beta:alpha2 receptor ratio cannot be changed. Also, beta3 receptor is the one responsible for lipolysis--which HGH through its mechanisms addresses. So, perhaps the best we can do is stimulate beta3's, block alpha 2's, and do liposuction on the remaining stubborn fat.

 

[nandi12]

Yes. In any case, I had no idea that the renin-angiotensin system was even involved in adipocyte development. Thanks again for your first post; it opened lots of doors.