The cardiovascular and renal functional responses to the 5-HT1A receptor agonist flesinoxan in two rat models of hypertension.
1. This study investigated the importance of renal sympathetic nerves in regulating sodium and water excretion from the kidneys of stroke prone spontaneously hypertensive and 2K1C Goldblatt hypertensive rats anaesthetized with chloralose/urethane (17.5/300 mg initially and supplemented at regular intervals), and prepared for measurement of renal function. 2. In stroke prone spontaneously hypertensive rats, flesinoxan, 30-1000 micrograms kg-1, i.v., caused graded reductions in blood pressure and heart rate of 74 +/- 5 mmHg and 63 +/- 9 beats min-1, respectively at the highest dose (P < 0.001). Renal blood flow did not change at any dose of drug while glomerular filtration rate fell by some 20% (P < 0.001) at the highest dose of drug, absolute and fractional sodium excretions, approximately doubled at 100 micrograms kg-1, and thereafter fell to below the baseline level at 1000 micrograms kg-1. 3. This pattern of excretory response was abolished following acute renal denervation when flesinoxan caused dose-related reductions in urine flow and sodium excretion, similar to that obtained by a mechanical reduction of renal perfusion pressure. 4. Flesinoxan administration (30-1000 micrograms kg-1, i.v.) into 2K1C Goldblatt hypertensive rats caused a maximum decrease in blood pressure and heart rate (both P < 0.001) of 34 +/- 3 mmHg and 20 +/- 6 beats min-1 and while renal blood flow and glomerular filtration rate were autoregulated, from 160 to 125 mmHg, there were dose-related decreases in urine volume and sodium excretion from the clipped and non-clipped kidneys of approximately 50-60% at the highest dose. 5. These findings suggest that in the stroke prone spontaneously hypertensive rat the renal nerves importantly control sodium and water reabsorption at the level of the tubules, whereas in 2K1C Goldblatt hypertensive rats, they play a minor role.
Chamienia
A L
AL
Department of Physiology, Medical School, Birmingham.
Johns
E J
EJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D010879:Piperazines; C056895:flesinoxan