Renal vascular responses in spontaneously hypertensive rats chronically treated with manidipine.
An enhanced renal vasoconstrictive response to emotional stress may be related to the pathogenesis of essential hypertension. We examined the effects of chronic manidipine treatment on renal blood flow (RBF) responses to air jet stress, angiotensin II (ANG II), and endothelin-3 (ET-3) in the conscious unrestrained spontaneously hypertensive rat (SHR). Male SHRs were placed on a control diet or one containing 0.05% of manidipine for 4 weeks. Age-matched Wistar-Kyoto (WKY) rats placed on a control diet served as normotensive controls. In comparison with control SHRs, manidipine reduced blood pressure (p < 0.01), increased urinary sodium excretion (p < 0.01), and reduced body weight (p < 0.01). Air jet stress elevated arterial pressure and increased RBF. The pressor response was enhanced more in the control SHRs than in the WKY rats (p < 0.01) and was not altered by manidipine. The percent fall in RBF in the manidipine-treated SHRs (-16%) was less than that in the control SHRs (-30%, p < 0.05) and similar to that in the WKY rats (-18%). In contrast, the pressor effect and the percent fall in RBF caused by ANG II (0.1 nmol/kg/min) were similar in the three groups. Intravenous ET-3 (1 nmol/kg) caused a transient fall, followed by a sustained increase in systemic blood pressure, both of which were associated with a decrease in RBF. The RBF response to ET-3 was blunted in SHRs compared to WKYs and was not altered by manidipine treatment. These results suggest that antihypertensive therapy with manidipine may be beneficial in maintaining RBF during emotional stress.
Muratani
H
H
Third Department of Internal Medicine, School of Medicine, University of The Ryukyus, Okinawa, Japan.
Takishita
S
S
Kawazoe
N
N
Tozawa
M
M
Fukiyama
K
K
D000399:Air Pressure; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000652:urine; D013312:Stress, Physiological / Q000150:complications / Q000209:etiology / Q000503:physiopathology; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology; D013997:Time Factors
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016232:Endothelins; D009578:Nitrobenzenes; D010879:Piperazines; D000804:Angiotensin II; C054218:manidipine; D012964:Sodium