PubMed · 7016423
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D L Horwitz. 1981. Renin.. https://pubmed.ncbi.nlm.nih.gov/7016423/
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Although it is well known that mechanical load to cardiac muscles causes cardiac hypertrophy, little is known about how mechanical load is transduced into the activation of intracellular signals which are linked to cell growth. We investigated whether the cardiac renin-angiotensin system was involved in stretch-induced hypertrophy of cultured neonatal rat heart myocytes. Myocytes were cultured with serum-free medium in a deformable silicon dish. Stretch of cardiac myocytes significantly increased the protein/DNA ratio at culture days 6 and 7, and the RNA/DNA ratio at culture days 4 and 5. Stretch significantly accelerated rates of protein synthesis by 15%. c-fos mRNA expression was significantly increased after stretch. The stimulatory effects of cell stretch on these parameters were significantly inhibited by the angiotensin converting enzyme inhibitor, captopril, or the type 1 angiotensin II receptor antagonist, losartan. The concentrations of angiotensin I and angiotensin II in culture media were significantly increased by stretch. Stretch did not change the angiotensin converting enzyme activity. These studies demonstrate that mechanical stretch activates the cardiac renin-angiotensin system in a autocrine and paracrine system which acts as an initial mediator of the stretch-induced hypertrophic growth.
There is increasing evidence that neuropeptides have trophic functions during embryogenesis. We examined the ability of angiotensin II, substance P, somatostatin-28 and luteinising hormone-releasing hormone to influence neurite outgrowth from embryonic chick sympathetic neurons in culture. Nanomolar concentrations of angiotensin II inhibited neurite outgrowth, whereas the other peptides had no effect at similar concentrations. The effect of angiotensin II on neurite outgrowth is likely to be mediated by an atypical angiotensin receptor, as it was only weakly inhibited by [sar1,ala8]angiotensin II, and was not inhibited by losartan, an inhibitor of mammalian AT1 receptors, or PD123319, an AT2 inhibitor. Neurite outgrowth was also inhibited by angiotensin III and angiotensin IV but not by angiotensinogen I1-14. The study provides further evidence that angiotensin peptides, like classical neurotransmitters, may have trophic functions during embryogenesis.
The renin-angiotensin system, through the effects of angiotensin II, may be involved in the pathogenesis of essential hypertension and associated left ventricular hypertrophy. Treatment with angiotensin-converting enzyme inhibition (ACEI) lowers blood pressure and reduces left ventricular hypertrophy. ACEI, however, may not completely inhibit the production of angiotensin II and its effects, and adverse effects like cough and rise in creatinine have been associated with ACEI and reduced degradation of bradykinin. The first selective antagonist of the angiotensin II-1 (AT1) receptor, losartan, has recently been approved. The LIFE study has been started, in which 8,300 hypertensive patients with left ventricular hypertrophy in Scandinavia and the USA will be randomized to blinded treatment with either atenolol or losartan to compare the effects on cardiovascular morbidity and mortality over a period of five years.