Angiotensin Peptides in Spontaneously Hypertensive and Normotensive Donryu Rats

Abstract

The renin-angiotensin system has been implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). Given that SHR may have normal or suppressed plasma levels of renin and angiotensin peptides, we examined whether the tissue levels of angiotensin peptides are elevated in these rats. We measured angiotensin-(1-7) [Ang-(1-7)], Ang II, and Ang I in plasma, kidney, adrenal, heart, aorta, brown adipose tissue, lung, and brain of male SHR and normotensive Donryu rats at 6, 10, and 20 weeks of age. SHR had higher blood pressures and ratios of heart weight to body weight at all ages. Plasma renin levels of SHR were 13% to 32% of the levels of Donryu rats. Although plasma angiotensin-converting enzyme activity was lower in SHR than in Donryu rats, lung was the only SHR tissue with a reduced Ang II-Ang I ratio. Ang II levels in SHR adrenal were 24% to 42% of the levels of Donryu adrenal, and for SHR plasma, aorta, brown adipose tissue, and lung, Ang II levels were 38% to 93% of the levels of Donryu rats. For kidney and heart, Ang II levels were similar in SHR and Donryu rats at 6 weeks of age although suppressed in SHR at 10 and 20 weeks. Moreover, brain Ang II levels were higher in SHR than Donryu rats at 6 weeks of age and similar at 10 and 20 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Kidney Aminopeptidase A and Hypertension, Part I

“…32,33 Moreover, the cardiovascular effects due to an increase in the half-life of Ang II could, over time, be indistinguishable from the effects due to elevated synthesis of Ang II. A decrease in Ang II degradation in the kidneys from young SHR would be consistent with observations that young SHR are hypersensitive to Ang II injected into the renal artery 20,21 and that kidneys of young SHR have normal 4 or elevated 7 Ang II levels with depressed or normal, respectively, plasma renin activity. On the other hand, the levels of Ang II within the kidney have been reported to be lower in adult SHR relative to normotensive rats.…”

“…1,2 On the other hand, plasma renin activity and plasma angiotensin II (Ang II) levels are not consistently elevated during any given stage of development in SHR. [3][4][5][6][7] Likewise, although plasma Ang II is elevated in stroke-prone SHR, plasma renin, angiotensinogen, and Ang II do not cosegregate with elevated blood pressure. 8,9 It is now recognized that the tissue levels of components of the RAS are more reliable indices of functional activity than are plasma levels.…”

“…18 Likewise, the renal vasculature of SHR have been shown to be hypersensitive to Ang II. 19 -22 There is no agreement, however, as to whether Ang II levels 4,5,7,23 or Ang II receptors 19,24 -28 are altered during the development or maintenance of the hypertension. Young SHR have elevated proximal tubule sodium reabsorption that can be reduced by ACE inhibition, whereas sodium reabsorption from adult SHR proximal tubules is reduced.…”

“…On the other hand, the levels of Ang II within the kidney have been reported to be lower in adult SHR relative to normotensive rats. 4,7 Elevated degradation of Ang II within the kidney would be expected to decrease Ang II levels. Thus, decreased degradation of Ang II may be a contributing factor to the development of hypertension in SHR, whereas increased degradation of Ang II in SHR may be a mitigating factor.…”

Role of the Angiotensin AT 1 Receptor in Rat Aortic and Cardiac PAI-1 Gene Expression

“…Plasma and tissue levels of Ang II appear similar in the SHR and normotensive control rats. 36 However, it is possible that local cellular increases in Ang II production contribute to an enhanced Ang II action in an autocrine/paracrine manner. Recent studies have shown that cultured vascular smooth muscle cells from SHRs are capable of generating Ang II, which leads to autocrine stimulation of AT 1 receptors, whereas Ang II production was undetectable in vascular smooth muscle cell cultures from WKY rats.…”