Endothelium-dependent, muscarinic receptor mediated vasodilator responses to bovine and human serum albumin

Urmila A. Shinde*, Banafsheh Moazed & Venkat Gopalakrishnan. Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK., S7N 5E5 Canada.

The effect of bovine serum albumin (BSA) on vascular reactivity was assessed in phenylephrine (PE) constricted aortic rings (RA), mesenteric vascular bed (MVB) and the third degree branches of the mesenteric arterioles (RMA, inner diameter ~ 100 µm) that were isolated from 14 week old male Sprague-Dawley rats using methods described earlier (1-2).

While BSA per se did not affect the basal vascular tone, it evoked concentration-dependent vasodilatation in PE constricted vessels. The pooled data (mean ± SEM) from several experiments performed using each preparation are shown. RA rings, EC50: 0.20 ± 0.09 g%, Emax: 80.1 ± 6.5%; MVB, EC50: 0.14 ± 0.01 g%, Emax: 67.1 ± 2.5%; RMA, EC50: 0.023 ± 0.01 g%, Emax: 78.3 ± 6.7%. The responses to BSA were absent in endothelium-denuded preparations. Inclusion of a nitric oxide synthase inhibitor, L-NAME (10 µM), significantly inhibited the vasodilator responses to BSA in RA rings and MVB with diminution of Emax values by about 15-20%. While the cyclooxygenase inhibitor, indomethacin (10 µM), did not produce any significant effect, the inclusion of a combination of apamin and charybdotoxin (100 nM each) that blocks endothelium-derived hyperpolarizing factor, partially inhibited the responses to BSA in these preparations. The inclusion of low concentrations of atropine (between 5 and 10 nM) led to a significant rightward shift in the concentration-response curve to BSA in all the three preparations. This effect was reversible upon removal of atropine. Human serum albumin also elicited vasodilatation, however, with lower efficacy compared to BSA or fatty acid free BSA (RA, Emax: 46.0 ± 3.6 %; MVB, Emax: 41.0 ± 6.5%). Fatty acid free BSA (0.001-1 g%) also evoked a similar degree of vasodilatation like BSA in all the three preparations. Intravenous administration of BSA (0.01-1 g%), however, did not evoke any major changes in the mean arterial pressure of rats anesthetized with intraperitoneal injection of thiopental sodium (100 mg kg-1; 3).

These data suggest that serum albumin could interact with muscarinic receptors present on the vascular endothelium and contribute to the regulation of vascular smooth muscle tone. Fatty acids in albumin may not contribute to the observed responses. Caution must be exercised in using BSA as an adjunct in characterizing vascular actions of exogenous peptides.

Pooled Data from Concentration–Response Curves to BSA (n > 6).

ND: Not Determined. * P < 0.01 compared to Control Endo (+) Group.

Chen, L. et al. (1995) Br J Pharmacol 114,1599-1604.
Misurski, DA. et al. (2001) Hypertension 37, 1298-1302.
Shinde, UA. et al. (2005) J Hypertens 23, 779-784.