thioinosine and Hypertension

The nucleoside transport system (NTS), an integral part of the adenosine inactivation mechanism, is physiologically significant in adenosine-mediated autoregulation of cardiovascular function. Radioreceptor approaches have been employed in the characterization of nucleoside transporters as potential targets in the therapy of cardiovascular diseases. Unanswered questions that are being addressed relate to their pharmacological regulation and their involvement in the pathogenesis of disease states. A brief overview of the characterization of nucleoside transporters in the cardiovascular system is presented and discussed in terms of their relevance to cardiovascular function.

Topics: Animals; Cardiovascular Physiological Phenomena; Carrier Proteins; Hypertension; Membrane Proteins; Nucleoside Transport Proteins; Radioligand Assay; Thioinosine; Tritium

We investigated the effects of dietary MaxEPA (a major source of eicosapentaenoic acid in fish oil) supplementation on blood pressure (BP) responses and heart rate (HR) of Dahl salt-sensitive (SS) rats fed low (0.4% NaCl) and high (8.0% NaCl) sodium diets. During a four week treatment period, BP remained normotensive in rats on low salt diet but was significantly elevated in those on high salt diet, causing 50% mortality. MaxEPA diminished the BP elevation and prevented the high salt-induced mortality. HR was not affected by either salt diet alone but was reduced in the presence of MaxEPA. At the end of the treatment period, the distribution of [3H]nitrobenzylthioinosine ([3H]NBMPR) binding, a putative marker of adenosine transport and metabolism, was estimated in selected rat tissues in order to evaluate the role of the purinergic system in the BP lowering effect of MaxEPA. Maximal [3H]NBMPR binding capacity (Bmax) in the kidney and platelets were 39% and 82% lower, respectively, in rats on high salt diet than in those on low salt diet. MaxEPA significantly blunted the decrease in Bmax in the kidney but not in platelets and increased Bmax in heart (48%) of low salt group. There were no changes in dissociation constants (Kd). The results suggest that MaxEPA can attenuate salt-induced hypertension, reduce salt-induced mortality and protect the integrity of kidney NBMPR binding sites in salt-induced hypertension.

Topics: Affinity Labels; Animals; Binding Sites; Blood Platelets; Blood Pressure; Body Weight; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Heart Rate; Hypertension; Kidney; Male; Rats; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Thioinosine

In an attempt to investigate the role of nucleoside transporter function in the hypertensive state, we have compared the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR), a nucleoside transporter probe, in membranes prepared from platelet, renal, pulmonary, cardiac and brain tissues of spontaneously hypertensive rats (SHR) to those of age-matched Wistar-Kyoto (WKY) controls. At 4 weeks of age, [( 3H]NBMPR) binding sites (Bmax) increased in the kidney of SHR but decreased in platelets, whereas no changes were found in the heart, lung or brain. At 18 weeks of age, [3H]NBMPR binding sites (Bmax) remained increased in the kidney and decreased in platelets with no changes in the other tissues. The only change in apparent binding affinity (KD) was an increase in the heart of SHR at 4 weeks. Age-dependent decreases were also observed in the heart and platelets of both SHR and WKY at 18 weeks. The results indicate that the changes in binding characteristics may be due to a combination of the pharmacodynamic differences between the strains, age, as well as to the pathogenesis of hypertension. Consequently, it cannot be concluded that the altered binding characteristics are the result of the elevated blood pressure.

Topics: Affinity Labels; Animals; Binding Sites; Blood Platelets; Blood Pressure; Brain; Hypertension; Inosine; Kidney; Least-Squares Analysis; Male; Myocardium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Regression Analysis; Thioinosine