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Effects of doxazosin on blood flow and mRNA expression of nitric oxide synthase in the spontaneously hypertensive rat genitourinary tract.

ABSTRACT: Hypertension may impact pelvic arterial blood flow resulting in reduction of nitric oxide synthase (NOS) levels. Although doxazosin, an alpha(1)-adrenoceptor antagonist, has been shown to improve erectile dysfunction as well as benign prostatic hyperplasia (BPH) and hypertension, it is not clear whether these improvements using doxazosin are primarily due to direct actions on the prostate, urinary bladder and penis, possibly via inhibition of vascular alpha(1)-adrenoceptors, or other sites of actions. Therefore, we investigated effects of doxazosin to the spontaneously hypertensive rat (SHR) on blood flow and NOS levels in the genitourinary tract. Four groups of rats were assessed: group 1, SHRs treated with doxazosin (30 mg/kg/day) for 4 weeks; group 2, SHRs treated with nifedipine (30 mg/kg/day) for 4 weeks; group 3, untreated SHRs; and group 4, untreated Wistar-Kyoto (WKY) rats. Blood flow to the ventral prostate, dorsolateral prostate, urinary bladder and penis was determined using a fluorescent microsphere infusion technique. Expression levels of nNOS and eNOS mRNAs were quantified by real-time RT-PCR using SYBR Green I. Blood flow to the ventral prostate, dorsolateral prostate, urinary bladder and penis was significantly lower in untreated SHRs than WKY rats. Treatment with doxazosin increased blood flow to each tissue studied in SHRs. RT-PCR data indicated that untreated SHRs had lower mRNA expression levels of nNOS in the bladder and penis and eNOS in the penis than WKY rats and that administration of doxazosin to the SHR caused an increase in expression levels of these genes, i.e., up-regulation of nNOS in the bladder and penis and eNOS in the penis. However, nifedipine had no significant effects on blood flow and NOS levels in the SHR genitourinary tract. Our data demonstrate that doxazosin treatment causes differential alterations in blood flow and NOS levels in the SHR genitourinary tract. These findings may provide insight into the beneficial effects of alpha(1)-adrenoceptor antagonists, on prostate, bladder and penile function, when used to treat symptoms of BPH and elevated blood pressure.

SUBMITTER: Yono M

PROVIDER: S-EPMC2077832 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Effects of doxazosin on blood flow and mRNA expression of nitric oxide synthase in the spontaneously hypertensive rat genitourinary tract.

Yono Makoto M Yamamoto Yasuhiro Y Yoshida Masaki M Ueda Shoichi S Latifpour Jamshid J

Life sciences 20070521 3

Hypertension may impact pelvic arterial blood flow resulting in reduction of nitric oxide synthase (NOS) levels. Although doxazosin, an alpha(1)-adrenoceptor antagonist, has been shown to improve erectile dysfunction as well as benign prostatic hyperplasia (BPH) and hypertension, it is not clear whether these improvements using doxazosin are primarily due to direct actions on the prostate, urinary bladder and penis, possibly via inhibition of vascular alpha(1)-adrenoceptors, or other sites of ac ...[more]

PMID: 17574276

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Project description:Background and purposeRapamycin is a clinically approved mammalian target of rapamycin inhibitor that has been shown to be neuroprotective in animal models of stroke. However, the mechanism of rapamycin-induced neuroprotection is still being explored. Our aims were to determine if rapamycin improved leptomeningeal collateral perfusion, to determine if this is through eNOS (endothelial nitric oxide synthase)-mediated vessel dilation and to determine if rapamycin increases immediate postreperfusion blood flow.MethodsWistar and spontaneously hypertensive rats (≈14 weeks old, n=22 and n=15, respectively) were subjected to ischemia by middle cerebral artery occlusion (90 and 120 minutes, respectively) with or without treatment with rapamycin at 30-minute poststroke. Changes in middle cerebral artery and collateral perfusion territories were measured by dual-site laser Doppler. Reactivity to rapamycin was studied using isolated and pressurized leptomeningeal anastomoses. Brain injury was measured histologically or with triphenyltetrazolium chloride staining.ResultsIn Wistar rats, rapamycin increased collateral perfusion (43±17%), increased reperfusion cerebral blood flow (16±8%) and significantly reduced infarct volume (35±6 versus 63±8 mm3, P<0.05). Rapamycin dilated leptomeningeal anastomoses by 80±9%, which was abolished by nitric oxide synthase inhibition. In spontaneously hypertensive rats, rapamycin increased collateral perfusion by 32±25%, reperfusion cerebral blood flow by 44±16%, without reducing acute infarct volume 2 hours postreperfusion. Reperfusion cerebral blood flow was a stronger predictor of brain damage than collateral perfusion in both Wistar and spontaneously hypertensive rats.ConclusionsRapamycin increased collateral perfusion and reperfusion cerebral blood flow in both Wistar and comorbid spontaneously hypertensive rats that appeared to be mediated by enhancing eNOS activation. These findings suggest that rapamycin may be an effective acute therapy for increasing collateral flow and as an adjunct therapy to thrombolysis or thrombectomy to improve reperfusion blood flow.

Dataset Information

Effects of doxazosin on blood flow and mRNA expression of nitric oxide synthase in the spontaneously hypertensive rat genitourinary tract.

Publications

Effects of doxazosin on blood flow and mRNA expression of nitric oxide synthase in the spontaneously hypertensive rat genitourinary tract.

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