Effects of salt loading and nitrendipine on dihydropyridine receptors in hypertensive rats.
It has already been emphasized that salt-dependent hypertension might be especially sensitive to calcium antagonists, and it has recently been shown that binding at different receptor types might be altered by dietary sodium chloride. Therefore, it was of interest to find the extent to which the specific membrane-associated dihydropyridine (DHP) receptors are influenced by salt loading and/or nitrendipine treatment. Groups of 10-12 salt-sensitive (S/JR) or salt-resistant (R/JR) Dahl rats and spontaneously hypertensive rats (SHRSP) or normotensive Wistar-Kyoto rats (WKY) received diets containing low (0.4%) or high (8%) NaCl for 21 days; treated animals received 300 ppm nitrendipine additionally with the diet. Blood pressure of R/JR and WKY did not differ markedly on the different diets, whereas in hypertensive rat strains, salt loading increased blood pressure after 3 weeks. High salt resulted in an increased number of cardiac DHP receptors in SHRSP; the addition of nitrendipine enhanced DHP receptor capacity in the heart and brain membranes of both strains (SHRSP and S/JR). No major changes in affinity were observed. Augmentation in the number of DHP receptors as analyzed in a follow-up interim observation study on SHR occurred more rapidly in heart than in brain tissue. It can be concluded that an altered number of the DHP receptor sites, and not changes in affinity, might be essential during treatment with calcium antagonists. The DHP receptor sites, and not changes in affinity, might be essential during treatment with calcium antagonists. The DHP receptor density can be modified by high salt intake, as shown in salt-loaded SHRSP.
Garthoff
B
B
Institute of Pharmacology, Bayer AG, Wuppertal, F.R.G.
Bellemann
P
P
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels; D006973:Hypertension / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009553:Nimodipine / Q000493:pharmacokinetics; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D012982:Sodium, Dietary; D009553:Nimodipine; D009568:Nitrendipine